Stomata function as the gates between the plant and the atmospheric environment. Stomatal movement, including stomatal opening and closing, controls CO2 absorption as the raw material for photosynthesis and water loss...Stomata function as the gates between the plant and the atmospheric environment. Stomatal movement, including stomatal opening and closing, controls CO2 absorption as the raw material for photosynthesis and water loss through transpiration. How to reduce water loss and maintain enough CO2 absorption has been an interesting research topic for some time. Simple stomatal opening may elevate CO2 absorption, but, in the meantime, promote the water loss, whereas simple closing of stomatal pores may reduce both water loss and CO2 absorption, resulting in impairment of plant photosynthesis. Both processes are not economical to the plant. As a special rhythmic stomatal movement that usually occurs at smaller stomatal apertures, stomatal oscillation can keep CO2 absorption at a sufficient level and reduce water loss at the same time, suggesting a potential improvement in water use efficiency. Stomatal oscillation is usually found after a sudden change in one environmental factor in relatively constant environments. Many environmental stimuli can induce stomatal oscillation. It appears that, at the physiological level, feedback controls are involved in stomatal oscillation. At the cellular level, possibly two different patterns exist： （i） a quicker responsive pattern; and （ii） a slower response. Both involve water potential changes and water channel regulation, but the mechanisms of regulation of the two patterns are different. Some evidence suggests that the regulation of water channels may play a vital and primary role in stomatal oscillation. The present review summarizes studies on stomatal oscillation and concludes with some discussion regarding the mechanisms of regulation of stomatal oscillation.展开更多
The development of the CNS in vertebrate embryos involves the generation of different sub-types of neurons and glia in a complex but highly-ordered spatio-temporal manner. Zebrafish are commonly used for exploring the...The development of the CNS in vertebrate embryos involves the generation of different sub-types of neurons and glia in a complex but highly-ordered spatio-temporal manner. Zebrafish are commonly used for exploring the development, plasticity and regeneration of the CNS, and the recent development of reliable protocols for isolating and culturing neural stem/progenitor cells(NSCs/NPCs) from the brain of adult fish now enables the exploration of mechanisms underlying the induction/specification/differentiation of these cells. Here, we refined a protocol to generate proliferating and differentiating neurospheres from the entire brain of adult zebrafish. We demonstrated via RT-qPCR that some isoforms of ip3 r, ryr and stim are upregulated/downregulated significantly in differentiating neurospheres, and via immunolabelling that 1,4,5-inositol trisphosphate receptor(IP3 R) type-1 and ryanodine receptor(RyR) type-2 are differentially expressed in cells with neuron-or radial glial-like properties. Furthermore, ATP but not caffeine(IP3 R and RyR agonists, respectively), induced the generation of Ca^(2+) transients in cells exhibiting neuron-or glial-like morphology. These results indicate the differential expression of components of the Ca^(2+) -signaling toolkit in proliferating and differentiating cells. Thus, given the complexity of the intact vertebrate brain, neurospheres might be a useful system for exploring neurodegenerative disease diagnosis protocols and drug development using Ca^(2+) signaling as a read-out.展开更多
Alterations in cellular calcium(Ca^(2+))signals have been causally associated with the development and progression of human cancers.Cellular Ca^(2+)signals are generated by channels,pumps,and exchangers that move Ca^(...Alterations in cellular calcium(Ca^(2+))signals have been causally associated with the development and progression of human cancers.Cellular Ca^(2+)signals are generated by channels,pumps,and exchangers that move Ca^(2+)ions across membranes and are decoded by effector proteins in the cytosol or in organelles.S-acylation,the reversible addition of 16-carbon fatty acids to proteins,modulates the activity of Ca^(2+)transporters by altering their affinity for lipids,and enzymes mediating this reversible post-translational modification have also been linked to several types of cancers.Here,we compile studies reporting an association between Ca^(2+)transporters or S-acylation enzymes with specific cancers,as well as studies reporting or predicting the S-acylation of Ca^(2+)transporters.We then discuss the potential role of S-acylation in the oncogenic potential of a subset of Ca^(2+)transport proteins involved in cancer.展开更多
Dysglycemia causes arterial endothelial damage,which is an early critical event in vascular complications for diabetes patients.Physiologically,moderate shear stress(SS)helps maintain endothelial cell health and norma...Dysglycemia causes arterial endothelial damage,which is an early critical event in vascular complications for diabetes patients.Physiologically,moderate shear stress(SS)helps maintain endothelial cell health and normal function.Reactive oxygen species(ROS)and calcium ions(Ca^(2+))signals are involved in dysglycemia-induced endothelial dysfunction and are also implicated in SS-mediated regulation of endothelial cell function.Therefore,it is urgent to establish in vitro models for studying endothelial biomechanics and mechanobiology,aiming to seek interventions that utilize appropriate SS to delay or reverse endothelial dysfunction.Microfluidic technology,as a novel approach,makes it possible to replicate blood glucose environment and accurate pulsatile SS in vitro.Here,we reviewed the progress of microfluidic systems used for SS-mediated repair of dysglycemia-induced endothelial cell damage(ECD),revealing the crucial roles of ROS and Ca^(2+)during the processes.It holds significant implications for finding appropriate mechanical intervention methods,such as exercise training,to prevent and treat cardiovascular complications in diabetes.展开更多
Objective To evaluate the chemical composition and effects of Artemisia vulgaris(AV)hydroalcoholic extract(HEAV)on breast cancer cells(MCF-7 and SKBR-3),chronic myeloid leukemia(K562)and NIH/3T3 fibroblasts.Methods Ph...Objective To evaluate the chemical composition and effects of Artemisia vulgaris(AV)hydroalcoholic extract(HEAV)on breast cancer cells(MCF-7 and SKBR-3),chronic myeloid leukemia(K562)and NIH/3T3 fibroblasts.Methods Phytochemical analysis of HEAV was done by high-performance liquid chromatography-mass(HPLC)spectrometry.Viability and cell death studies were performed using trypan blue and Annexin/FITC-7AAD,respectively.Ferrostatin-1(Fer-1)and necrostatin-1(Nec-1)were used to assess the mode of HEAV-induced cell death and acetoxymethylester(BAPTA-AM)was used to verify the involvement of cytosolic calcium in this event.Cytosolic calcium measurements were made using Fura-2-AM.Results HEAV decreased the viability of MCF-7,SKBR-3 and K562 cells(P<0.05).The viability of HEAV-treated K562 cells was reduced compared to HEAV-exposed fibroblasts(P<0.05).Treatment of K562 cells with HEAV induced cell death primarily by late apoptosis and necrosis in assays using annexin V-FITC/7-AAD(P<0.05).The use of Nec-1 and Fer-1 increased the viability of K562 cells treated with HEAV relative to cells exposed to HEAV alone(P<0.01).HEAV-induced Ca^(2+)release mainly from lysosomes in K562 cells(P<0.01).Furthermore,BAPTA-AM,an intracellular Ca^(2+)chelator,decreased the number of non-viable cells treated with HEAV(P<0.05).Conclusions HEAV is cytotoxic and activates several modalities of cell death,which are partially dependent on lysosomal release of Ca^(2+).These effects may be related to artemisinin and caffeoylquinic acids,the main compounds identified in HEAV.展开更多
Proximal tubule(PT)transports most of the renal Ca^(2+),which was usually described as paracellular(passive).We found a regulated Ca^(2+)entry pathway in PT cells via the apical transient receptor potential canonical ...Proximal tubule(PT)transports most of the renal Ca^(2+),which was usually described as paracellular(passive).We found a regulated Ca^(2+)entry pathway in PT cells via the apical transient receptor potential canonical 3(TRPC3)channel,which initiates transcellular Ca^(2+)transport.Although TRPC3 knockout(−/−)mice were mildly hypercalciuric and displayed luminal calcium phosphate(CaP)crystals at Loop of Henle(LOH),no CaP+calcium oxalate(CaOx)mixed urine crystals were spotted,which are mostly found in calcium nephrolithiasis(CaNL).Thus,we used oral calcium gluconate(CaG;2%)to raise the PT luminal[Ca^(2+)]o further in TRPC3−/−mice for developing such mixed stones to understand the mechanistic role of PT-Ca^(2+)signaling in CaNL.Expectedly,CaG-treated mice urine samples presented with numerous mixed crystals with remains of PT cells,which were pronounced in TRPC3−/−mice,indicating PT cell damage.Notably,PT cells from CaG-treated groups switched their mode of Ca^(2+)entry from receptor-operated to store-operated pathway with a sustained rise in intracellular[Ca^(2+)]([Ca^(2+)]i),indicating the stagnation in PT Ca^(2+)transport.Moreover,those PT cells from CaG-treated groups demonstrated an upregulation of calcification,inflammation,fibrotic,oxidative stress,and apoptotic genes;effects of which were more robust in TRPC3 ablated condition.Furthermore,kidneys from CaG-treated groups exhibited fibrosis,tubular injury and calcifications with significant reactive oxygen species generation in the urine,thus,indicating in vivo CaNL.Taken together,excess PT luminal Ca^(2+)due to escalation of hypercalciuria in TRPC3 ablated mice induced surplus CaP crystal formation and caused stagnation of PT[Ca^(2+)]i,invoking PT cell injury,hence mixed stone formation.展开更多
The nuclear envelope is increasingly viewed from an electrophysiological perspective by researchers interested in signal transduction pathways that influence gene transcription and other processes in the nucleus. Here...The nuclear envelope is increasingly viewed from an electrophysiological perspective by researchers interested in signal transduction pathways that influence gene transcription and other processes in the nucleus. Here, we describe evidence for ion channels and transporters in the nuclear membranes and for possible ion gating by the nuclear pores. We argue that a systems-level understanding of cellular regulation is likely to require the assimilation of nuclear electrophysiology into molecular and biochemical signaling pathways.展开更多
This brief article highlights the results of Fu et al.(Proc Natl Acad Sci USA 119:e2204574119,2022),who recently found that manganese(Mn)deficiency triggers long-lasting multicellular Ca^(2+) oscillations in the elong...This brief article highlights the results of Fu et al.(Proc Natl Acad Sci USA 119:e2204574119,2022),who recently found that manganese(Mn)deficiency triggers long-lasting multicellular Ca^(2+) oscillations in the elongation zone(EZ)of Arabidopsis roots and revealed a Ca^(2+)-CPK21/23-NRAMP1 axis as an important mechanism for plant tolerance and adaptation to low Mn.展开更多
Stem cells hold indefinite self-renewable capability that can be differentiated into all desired cell types.Based on their plasticity potential,they are divided into totipotent(morula stage cells),pluripotent(embryoni...Stem cells hold indefinite self-renewable capability that can be differentiated into all desired cell types.Based on their plasticity potential,they are divided into totipotent(morula stage cells),pluripotent(embryonic stem cells),multipotent(hematopoietic stem cells,multipotent adult progenitor stem cells,and mesenchymal stem cells[MSCs]),and unipotent(progenitor cells that differentiate into a single lineage)cells.Though bone marrow is the primary source of multipotent stem cells in adults,other tissues such as adipose tissues,placenta,amniotic fluid,umbilical cord blood,periodontal ligament,and dental pulp also harbor stem cells that can be used for regenerative therapy.In addition,induced pluripotent stem cells also exhibit fundamental properties of self-renewal and differentiation into specialized cells,and thus could be another source for regenerative medicine.Several diseases including neurodegenerative diseases,cardiovascular diseases,autoimmune diseases,virus infection(also coronavirus disease 2019)have limited success with conventional medicine,and stem cell transplantation is assumed to be the best therapy to treat these disorders.Importantly,MSCs,are by far the best for regenerative medicine due to their limited immune modulation and adequate tissue repair.Moreover,MSCs have the potential to migrate towards the damaged area,which is regulated by various factors and signaling processes.Recent studies have shown that extracellular calcium(Ca^(2+))promotes the proliferation of MSCs,and thus can assist in transplantation therapy.Ca^(2+)signaling is a highly adaptable intracellular signal that contains several components such as cell-surface receptors,Ca^(2+)channels/pumps/exchangers,Ca^(2+)buffers,and Ca^(2+)sensors,which together are essential for the appropriate functioning of stem cells and thus modulate their proliferative and regenerative capacity,which will be discussed in this review.展开更多
Mast cells(MCs)play an important role in the immune system.Through connective tissues,mechanical stimuli activate intracellular calcium signaling pathways,induce a variety of mediators including leukotriene C4(LTC4)re...Mast cells(MCs)play an important role in the immune system.Through connective tissues,mechanical stimuli activate intracellular calcium signaling pathways,induce a variety of mediators including leukotriene C4(LTC4)release,and affect MCs’microenvironment.This paper focuses on MCs’intracellular calcium dynamics and LTC4 release responding to mechanical stimuli,explores signaling pathways in MCs and the effect of interstitial fluid flow on the transport of biological messengers and feedback in the MCs network.We use a mathematical model to show that(i)mechanical stimuli including shear stress induced by interstitial fluid flow can activate mechano-sensitive(MS)ion channels on MCs’membrane and allow Ca^(2+)entry,which increases intracellular Ca^(2+)concentration and leads to LTC4 release;(ii)LTC4 in the extracellular space(ECS)acts on surface cysteinyl leukotriene receptors(LTC4R)on adjacent cells,leading to Ca^(2+)influx through Ca^(2+)release-activated Ca^(2+)(CRAC)channels.An elevated intracellular Ca^(2+)concentration further stimulates LTC4 release and creates a positive feedback in the MCs network.The findings of this study may facilitate our understanding of the mechanotransduction process in MCs induced by mechanical stimuli,contribute to understanding of interstitial flow-related mechanobiology in MCs network,and provide a methodology for quantitatively analyzing physical treatment methods including acupuncture and massage in traditional Chinese medicine(TCM).展开更多
基金supported by grants from the Hong Kong Research Grant Committee Theme-based Research Scheme(TBRS)(T13-706/11,AoE/M-05/12,CUHK2/CRF/11G,CUHK478011,CUHK478413)the National Natural Science Foundation of China(No.31171100)
文摘Stomata function as the gates between the plant and the atmospheric environment. Stomatal movement, including stomatal opening and closing, controls CO2 absorption as the raw material for photosynthesis and water loss through transpiration. How to reduce water loss and maintain enough CO2 absorption has been an interesting research topic for some time. Simple stomatal opening may elevate CO2 absorption, but, in the meantime, promote the water loss, whereas simple closing of stomatal pores may reduce both water loss and CO2 absorption, resulting in impairment of plant photosynthesis. Both processes are not economical to the plant. As a special rhythmic stomatal movement that usually occurs at smaller stomatal apertures, stomatal oscillation can keep CO2 absorption at a sufficient level and reduce water loss at the same time, suggesting a potential improvement in water use efficiency. Stomatal oscillation is usually found after a sudden change in one environmental factor in relatively constant environments. Many environmental stimuli can induce stomatal oscillation. It appears that, at the physiological level, feedback controls are involved in stomatal oscillation. At the cellular level, possibly two different patterns exist： （i） a quicker responsive pattern; and （ii） a slower response. Both involve water potential changes and water channel regulation, but the mechanisms of regulation of the two patterns are different. Some evidence suggests that the regulation of water channels may play a vital and primary role in stomatal oscillation. The present review summarizes studies on stomatal oscillation and concludes with some discussion regarding the mechanisms of regulation of stomatal oscillation.
基金supported by the ANR/RGC Joint Research Scheme Award (A-HKUST601/ 13)the HK RGC General Research Fund awards (662113, 16101714, 16100115)Funding from the HKITC (ITCPD/17-9)
文摘The development of the CNS in vertebrate embryos involves the generation of different sub-types of neurons and glia in a complex but highly-ordered spatio-temporal manner. Zebrafish are commonly used for exploring the development, plasticity and regeneration of the CNS, and the recent development of reliable protocols for isolating and culturing neural stem/progenitor cells(NSCs/NPCs) from the brain of adult fish now enables the exploration of mechanisms underlying the induction/specification/differentiation of these cells. Here, we refined a protocol to generate proliferating and differentiating neurospheres from the entire brain of adult zebrafish. We demonstrated via RT-qPCR that some isoforms of ip3 r, ryr and stim are upregulated/downregulated significantly in differentiating neurospheres, and via immunolabelling that 1,4,5-inositol trisphosphate receptor(IP3 R) type-1 and ryanodine receptor(RyR) type-2 are differentially expressed in cells with neuron-or radial glial-like properties. Furthermore, ATP but not caffeine(IP3 R and RyR agonists, respectively), induced the generation of Ca^(2+) transients in cells exhibiting neuron-or glial-like morphology. These results indicate the differential expression of components of the Ca^(2+) -signaling toolkit in proliferating and differentiating cells. Thus, given the complexity of the intact vertebrate brain, neurospheres might be a useful system for exploring neurodegenerative disease diagnosis protocols and drug development using Ca^(2+) signaling as a read-out.
基金Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung(Grant/Award Number:310030_189042)。
文摘Alterations in cellular calcium(Ca^(2+))signals have been causally associated with the development and progression of human cancers.Cellular Ca^(2+)signals are generated by channels,pumps,and exchangers that move Ca^(2+)ions across membranes and are decoded by effector proteins in the cytosol or in organelles.S-acylation,the reversible addition of 16-carbon fatty acids to proteins,modulates the activity of Ca^(2+)transporters by altering their affinity for lipids,and enzymes mediating this reversible post-translational modification have also been linked to several types of cancers.Here,we compile studies reporting an association between Ca^(2+)transporters or S-acylation enzymes with specific cancers,as well as studies reporting or predicting the S-acylation of Ca^(2+)transporters.We then discuss the potential role of S-acylation in the oncogenic potential of a subset of Ca^(2+)transport proteins involved in cancer.
基金supported by the National Natural Science Foundation of China(grant numbers 12372304,12172081)。
文摘Dysglycemia causes arterial endothelial damage,which is an early critical event in vascular complications for diabetes patients.Physiologically,moderate shear stress(SS)helps maintain endothelial cell health and normal function.Reactive oxygen species(ROS)and calcium ions(Ca^(2+))signals are involved in dysglycemia-induced endothelial dysfunction and are also implicated in SS-mediated regulation of endothelial cell function.Therefore,it is urgent to establish in vitro models for studying endothelial biomechanics and mechanobiology,aiming to seek interventions that utilize appropriate SS to delay or reverse endothelial dysfunction.Microfluidic technology,as a novel approach,makes it possible to replicate blood glucose environment and accurate pulsatile SS in vitro.Here,we reviewed the progress of microfluidic systems used for SS-mediated repair of dysglycemia-induced endothelial cell damage(ECD),revealing the crucial roles of ROS and Ca^(2+)during the processes.It holds significant implications for finding appropriate mechanical intervention methods,such as exercise training,to prevent and treat cardiovascular complications in diabetes.
基金Supported by the São Paulo Research Foundation[FAPESP,No.2020/14406(CB)]Brazilian National Council for Scientific and Technological Development(CNPq,No.PQ-302148/2019-1)Coordination of Superior Level Staff Improvement(CAPES)。
文摘Objective To evaluate the chemical composition and effects of Artemisia vulgaris(AV)hydroalcoholic extract(HEAV)on breast cancer cells(MCF-7 and SKBR-3),chronic myeloid leukemia(K562)and NIH/3T3 fibroblasts.Methods Phytochemical analysis of HEAV was done by high-performance liquid chromatography-mass(HPLC)spectrometry.Viability and cell death studies were performed using trypan blue and Annexin/FITC-7AAD,respectively.Ferrostatin-1(Fer-1)and necrostatin-1(Nec-1)were used to assess the mode of HEAV-induced cell death and acetoxymethylester(BAPTA-AM)was used to verify the involvement of cytosolic calcium in this event.Cytosolic calcium measurements were made using Fura-2-AM.Results HEAV decreased the viability of MCF-7,SKBR-3 and K562 cells(P<0.05).The viability of HEAV-treated K562 cells was reduced compared to HEAV-exposed fibroblasts(P<0.05).Treatment of K562 cells with HEAV induced cell death primarily by late apoptosis and necrosis in assays using annexin V-FITC/7-AAD(P<0.05).The use of Nec-1 and Fer-1 increased the viability of K562 cells treated with HEAV relative to cells exposed to HEAV alone(P<0.01).HEAV-induced Ca^(2+)release mainly from lysosomes in K562 cells(P<0.01).Furthermore,BAPTA-AM,an intracellular Ca^(2+)chelator,decreased the number of non-viable cells treated with HEAV(P<0.05).Conclusions HEAV is cytotoxic and activates several modalities of cell death,which are partially dependent on lysosomal release of Ca^(2+).These effects may be related to artemisinin and caffeoylquinic acids,the main compounds identified in HEAV.
基金National Institute of Diabetes and Digestive and Kidney Diseases(No.DK102043)funding to B.C.B supported this study.
文摘Proximal tubule(PT)transports most of the renal Ca^(2+),which was usually described as paracellular(passive).We found a regulated Ca^(2+)entry pathway in PT cells via the apical transient receptor potential canonical 3(TRPC3)channel,which initiates transcellular Ca^(2+)transport.Although TRPC3 knockout(−/−)mice were mildly hypercalciuric and displayed luminal calcium phosphate(CaP)crystals at Loop of Henle(LOH),no CaP+calcium oxalate(CaOx)mixed urine crystals were spotted,which are mostly found in calcium nephrolithiasis(CaNL).Thus,we used oral calcium gluconate(CaG;2%)to raise the PT luminal[Ca^(2+)]o further in TRPC3−/−mice for developing such mixed stones to understand the mechanistic role of PT-Ca^(2+)signaling in CaNL.Expectedly,CaG-treated mice urine samples presented with numerous mixed crystals with remains of PT cells,which were pronounced in TRPC3−/−mice,indicating PT cell damage.Notably,PT cells from CaG-treated groups switched their mode of Ca^(2+)entry from receptor-operated to store-operated pathway with a sustained rise in intracellular[Ca^(2+)]([Ca^(2+)]i),indicating the stagnation in PT Ca^(2+)transport.Moreover,those PT cells from CaG-treated groups demonstrated an upregulation of calcification,inflammation,fibrotic,oxidative stress,and apoptotic genes;effects of which were more robust in TRPC3 ablated condition.Furthermore,kidneys from CaG-treated groups exhibited fibrosis,tubular injury and calcifications with significant reactive oxygen species generation in the urine,thus,indicating in vivo CaNL.Taken together,excess PT luminal Ca^(2+)due to escalation of hypercalciuria in TRPC3 ablated mice induced surplus CaP crystal formation and caused stagnation of PT[Ca^(2+)]i,invoking PT cell injury,hence mixed stone formation.
文摘The nuclear envelope is increasingly viewed from an electrophysiological perspective by researchers interested in signal transduction pathways that influence gene transcription and other processes in the nucleus. Here, we describe evidence for ion channels and transporters in the nuclear membranes and for possible ion gating by the nuclear pores. We argue that a systems-level understanding of cellular regulation is likely to require the assimilation of nuclear electrophysiology into molecular and biochemical signaling pathways.
基金supported by grants from National Natural Science Foundation of China(Grant No.31900216)National Key Laboratory of Plant Molecular Genetics.
文摘This brief article highlights the results of Fu et al.(Proc Natl Acad Sci USA 119:e2204574119,2022),who recently found that manganese(Mn)deficiency triggers long-lasting multicellular Ca^(2+) oscillations in the elongation zone(EZ)of Arabidopsis roots and revealed a Ca^(2+)-CPK21/23-NRAMP1 axis as an important mechanism for plant tolerance and adaptation to low Mn.
基金National Institute of Dental&Craniofacial Research,No.1R21DE028265-01A1.
文摘Stem cells hold indefinite self-renewable capability that can be differentiated into all desired cell types.Based on their plasticity potential,they are divided into totipotent(morula stage cells),pluripotent(embryonic stem cells),multipotent(hematopoietic stem cells,multipotent adult progenitor stem cells,and mesenchymal stem cells[MSCs]),and unipotent(progenitor cells that differentiate into a single lineage)cells.Though bone marrow is the primary source of multipotent stem cells in adults,other tissues such as adipose tissues,placenta,amniotic fluid,umbilical cord blood,periodontal ligament,and dental pulp also harbor stem cells that can be used for regenerative therapy.In addition,induced pluripotent stem cells also exhibit fundamental properties of self-renewal and differentiation into specialized cells,and thus could be another source for regenerative medicine.Several diseases including neurodegenerative diseases,cardiovascular diseases,autoimmune diseases,virus infection(also coronavirus disease 2019)have limited success with conventional medicine,and stem cell transplantation is assumed to be the best therapy to treat these disorders.Importantly,MSCs,are by far the best for regenerative medicine due to their limited immune modulation and adequate tissue repair.Moreover,MSCs have the potential to migrate towards the damaged area,which is regulated by various factors and signaling processes.Recent studies have shown that extracellular calcium(Ca^(2+))promotes the proliferation of MSCs,and thus can assist in transplantation therapy.Ca^(2+)signaling is a highly adaptable intracellular signal that contains several components such as cell-surface receptors,Ca^(2+)channels/pumps/exchangers,Ca^(2+)buffers,and Ca^(2+)sensors,which together are essential for the appropriate functioning of stem cells and thus modulate their proliferative and regenerative capacity,which will be discussed in this review.
基金supported by National Natural Science Foundation of China(No.81473750 and No.11202053)Shanghai Key Laboratory of Acupuncture Mechanis m And Acupoint Function(No.14DZ2260500)National Basic Research Program of China(No.2012CB518502).
文摘Mast cells(MCs)play an important role in the immune system.Through connective tissues,mechanical stimuli activate intracellular calcium signaling pathways,induce a variety of mediators including leukotriene C4(LTC4)release,and affect MCs’microenvironment.This paper focuses on MCs’intracellular calcium dynamics and LTC4 release responding to mechanical stimuli,explores signaling pathways in MCs and the effect of interstitial fluid flow on the transport of biological messengers and feedback in the MCs network.We use a mathematical model to show that(i)mechanical stimuli including shear stress induced by interstitial fluid flow can activate mechano-sensitive(MS)ion channels on MCs’membrane and allow Ca^(2+)entry,which increases intracellular Ca^(2+)concentration and leads to LTC4 release;(ii)LTC4 in the extracellular space(ECS)acts on surface cysteinyl leukotriene receptors(LTC4R)on adjacent cells,leading to Ca^(2+)influx through Ca^(2+)release-activated Ca^(2+)(CRAC)channels.An elevated intracellular Ca^(2+)concentration further stimulates LTC4 release and creates a positive feedback in the MCs network.The findings of this study may facilitate our understanding of the mechanotransduction process in MCs induced by mechanical stimuli,contribute to understanding of interstitial flow-related mechanobiology in MCs network,and provide a methodology for quantitatively analyzing physical treatment methods including acupuncture and massage in traditional Chinese medicine(TCM).
