Pancreatic cancer is one of the most aggressive and difficult cancers to treat.Despite numerous research efforts,limited success has been achieved in the therapeutic management of patients with this disease.In the cur...Pancreatic cancer is one of the most aggressive and difficult cancers to treat.Despite numerous research efforts,limited success has been achieved in the therapeutic management of patients with this disease.In the current review,we focus on one component of morphogenesis signaling,Hedgehog(Hh),with the aim of developing novel,effective therapies for the treatment of pancreatic cancer.Hh signaling contributes to the induction of a malignant phenotype in pancreatic cancer and is responsible for maintaining pancreatic cancer stem cells.In addition,we propose a novel concept linking Hh signaling and tumor hypoxic conditions,and discuss the effects of Hh inhibitors in clinical trials.The Hh signaling pathway may represent a potential therapeutic target for patients with refractory pancreatic cancer.展开更多
Background: Previous research suggested that insulin-like growth factor binding protein related protein 1(IGFBPrP1), as a novel mediator, contributes to hepatic fibrogenesis. Matrix metalloproteinases(MMP) and tissue ...Background: Previous research suggested that insulin-like growth factor binding protein related protein 1(IGFBPrP1), as a novel mediator, contributes to hepatic fibrogenesis. Matrix metalloproteinases(MMP) and tissue inhibitors of metalloproteinases(TIMP) play an essential role in hepatic fibrogenesis by regulating homeostasis and remodeling of the extracellular matrix(ECM). However, the interaction between IGFBPrP1 and MMP/TIMP is not clear. The present study was to knockdown IGFBPrP1 to investigate the correlation between IGFBPrP1 and MMP/TIMP in hepatic fibrosis. Methods: Hepatic fibrosis was induced by thioacetamide(TAA) in mice. Knockdown of IGFBPrP1 expression by ultrasound-targeted microbubble destruction-mediated CMB-shRNA-IGFBPrP1 delivery, or inhibition of the Hedgehog(Hh) pathway by cyclopamine treatment, was performed in TAA-induced liver fibrosis mice. Hepatic fibrosis was determined by hematoxylin and eosin and Sirius red staining. Hepatic expression of IGFBPrP1, α-smooth muscle actin( α-SMA), transforming growth factor β 1(TGF β1), collagen I, MMPs/TIMPs, Sonic Hedgehog(Shh), and glioblastoma family transcription factors(Gli1) were investigated by immunohistochemical staining and Western blotting analysis. Results: We found that hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I were increased longitudinally in mice with TAA-induced hepatic fibrosis, concomitant with MMP2/TIMP2 and MMP9/TIMP1 imbalance and Hh pathway activation. Knockdown of IGFBPrP1 expression, or inhibition of the Hh pathway, reduced the hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I and re-established MMP2/TIMP2 and MMP9/TIMP1 balance. Conclusions: Our findings suggest that IGFBPrP1 knockdown attenuates liver fibrosis by re-establishing MMP2/TIMP2 and MMP9/TIMP1 balance, concomitant with the inhibition of hepatic stellate cell activation, down-regulation of TGF β1 expression, and degradation of the ECM. Furthermore, the Hh pathway mediates IGFBPrP1 knockdown-induced attenuation of hepatic fibro展开更多
Colorectal cancer(CRC)represents the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide.The modern concept of cancer biology indicates that cancer is formed of a small populati...Colorectal cancer(CRC)represents the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide.The modern concept of cancer biology indicates that cancer is formed of a small population of cells called cancer stem cells(CSCs),which present both pluripotency and self-renewal properties.These cells are considered responsible for the progression of the disease,recurrence and tumor resistance.Interestingly,some cell signaling pathways participate in CRC survival,proliferation,and selfrenewal properties,and most of them are dysregulated in CSCs,including the Wingless(Wnt)/β-catenin,Notch,Hedgehog,nuclear factor kappa B(NF-κB),Janus kinase/signal transducer and activator of transcription(JAK/STAT),peroxisome proliferator-activated receptor(PPAR),phosphatidyl-inositol-3-kinase/Akt/mechanistic target of rapamycin(PI3K/Akt/mTOR),and transforming growth factor-β(TGF-β)/Smad pathways.In this review,we summarize the strategies for eradicating CRC stem cells by modulating these dysregulated pathways,which will contribute to the study of potential therapeutic schemes,combining conventional drugs with CSC-targeting drugs,and allowing better cure rates in anti-CRC therapy.展开更多
Background: The PTCH1 gene, also known as Patched 1, is located on the long arm of human chromosome 9 (9q22.3). It encodes the PTCH1 protein, which is a critical transmembrane receptor within the Hedgehog signaling pa...Background: The PTCH1 gene, also known as Patched 1, is located on the long arm of human chromosome 9 (9q22.3). It encodes the PTCH1 protein, which is a critical transmembrane receptor within the Hedgehog signaling pathway (Hh), playing a pivotal role in cellular communication and developmental processes. Recent studies have highlighted the significance of mutations in PTCH1 in the pathogenesis of lung cancer, positioning it as a crucial molecule for investigation in oncology. Purpose: This review aims to elucidate the role of the PTCH1 and the Hedgehog pathway in the initiation, progression, and potential treatment of lung cancer, thereby providing a theoretical foundation for personalized and precise therapeutic strategies. Method: To ensure a comprehensive review, this study systematically searched for literature related to the PTCH1, lung cancer, and the Hedgehog pathway across multiple databases including PubMed, Web of Science, and CNKI (China National Knowledge Infrastructure). The search strategy involved using specific keywords and advanced filtering options to include the most relevant and recent studies. Initial screening excluded irrelevant articles, followed by a detailed evaluation of the selected studies based on their scientific quality and relevance. Results: This review indicated that specific mutations in the PTCH1 gene are closely associated with the onset and progression of lung cancer. These mutations impede normal Hedgehog signaling, leading to unregulated cell proliferation and tumor growth. Targeting PTCH1, including vismodegib, have shown efficacy in clinical cases, particularly in SCCL with specific PTCH1 mutations, leading to complete remissions. Furthermore, the interaction between PTCH1 and microRNA-212 suggests potential therapeutic approaches by targeting miRNA to regulate PTCH1 expression. In addition, the investigation of traditional Chinese medicines such as Ginsenosides and Cordyceps sinensis extracts has shown their potential to modulate the Hedgehog pathway and reverse drug r展开更多
Hedgehog （Hh） signals regulate invertebrate and vertebrate development, yet the role of the pathway in adipose development remains poorly understood. In this report, we found that Hh pathway components are expressed...Hedgehog （Hh） signals regulate invertebrate and vertebrate development, yet the role of the pathway in adipose development remains poorly understood. In this report, we found that Hh pathway components are expressed in the fat body of silkworm larvae. Functional analysis of these components in a BmN cell line model revealed that activa- tion of the Hh gene stimulated transcription of Hh pathway components, but inhibited the expression of the adipose marker gene AP2. Conversely, specific RNA interference- mediated knockdown of Hh resulted in increased AP2 expression. This further showed the regulation of Hh signal on the adipose marker gene. In silkworm larval models, enhanced adipocyte differentiation and an increase in adipocyte cell size were observed in silkworms that had been treated with a specific Hh signaling pathway antagonist, cyclopamine. The fat-body-specific Hh blockade tests were consistent with Hh signaling inhibiting silkworm adipogenesis. Our results indicate that the role of Hh signaling in inhibiting fat formation is conserved in vertebrates and invertebrates.展开更多
Constitutive hedgehog （Hh） signaling is associated with the genesis of medulloblastomas （MB）. The objective of this study is to identify special microRNAs （miRNAs） regulated by the Hh pathway, and to clarify the...Constitutive hedgehog （Hh） signaling is associated with the genesis of medulloblastomas （MB）. The objective of this study is to identify special microRNAs （miRNAs） regulated by the Hh pathway, and to clarify the role of miRNAs during the genesis of MB induced by sustained Hh activation. In the primary screening, we used stemloop RT-PCR to test the expression of 90 different miRNAs in the wildtype （WT） and Ptc-/- MEF cell lines. In the secondary screening, the miRNAs screened from the first screening were validated in the Sufu-/- MEF cell lines. We then verified the expression of miRNAs both in the normal cerebellar tissues and the MB induced by activated Hh pathway, and examined the expression of the other 21 miRNA members of the miR-154 cluster in the MB and normal cerebellum. In the first screening, 13 miRNAs showed significant differential expression in WT and Ptc-/- MEF cell lines, while 10 of them had significant difference in the Sufu-/- MEF cell line. Compared to the normal mouse cerebellum, only 2 miRNAs in 15 miRNAs were differentially expressed between the MB and normal cerebellar tissues. Among 21 members of the miR-154 cluster, 6 miRNAs were downregulated in the MB. Our study demonstrated that miR-154 may be regulated by the Hh pathway, and the activation of the Hh pathway led to the downregulation of the miR-154 cluster, resulting in the genesis of MB.展开更多
Bone marrow-derived mesenchymal stem cells differentiate into neurons under the induction of Schwann cells. However, key microRNAs and related pathways for differentiation remain unclear. This study screened and ident...Bone marrow-derived mesenchymal stem cells differentiate into neurons under the induction of Schwann cells. However, key microRNAs and related pathways for differentiation remain unclear. This study screened and identified differentially expressed microRNAs in bone marrow- derived mesenchymal stem cells induced by Schwann cell-conditioned medium, and explored targets and related pathways involved in their differentiation into neuronal-like cells. Primary bone marrow-derived mesenchymal stem cells were isolated from femoral and tibial bones, while primary Schwann cells were isolated from bilateral saphenous nerves. Bone marrow-derived mesenchymal stem cells were cultured in unconditioned (control group) and Schwann cell-conditioned medium (bone marrow-derived mesenchymal stem cell + Schwann cell group). Neuronal differentiation of bone marrow-derived mesenchymal stem cells induced by Schwann cell-conditioned medium was observed by time-lapse imaging. Upon induction, the morphology of bone marrow-derived mesencaymal stem cells changed into a neural shape with neurites. Results of quantitative reverse transcription-polymerase chain reaction revealed that nestin mRNA expression was upregulated from 1 to 3 days and downregulated from 3 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. Compared with the control group, microtubule-associated protein 2 mRNA expression gradually increased from 1 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. After 7 days of induction, microRNA analysis iden:ified 83 significantly differentially expressed microRNAs between the two groups. Gene Ontology analysis indicated enrichment of microRNA target genes for neuronal projection development, regulation of axonogenesis, and positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that Hippo, Wnt, transforming growth factor-beta, and Hedgehog signaling pathv/ays were potentially associated with neural differentiation of b展开更多
Summary： The roles of Indian hedgehog （Ihh） signaling pathway in the proliferation and apoptosis of precartilaginous stem cells （PSCs） were investigated. PSCs, labeled with fibroblast growth factor receptor 3 （F...Summary： The roles of Indian hedgehog （Ihh） signaling pathway in the proliferation and apoptosis of precartilaginous stem cells （PSCs） were investigated. PSCs, labeled with fibroblast growth factor receptor 3 （FGFR-3）, were isolated from neonatal rats by immunomagnetic separation. After identification with FGFR-3 and Col II, the cells were incubated with different concentrations of cyclopamine （cyclo）, the specific inhibitor of Ihh signaling pathway. The morphologic changes of the cells were observed under the inverted phase contrast microscope. The mRNA expression levels of Ihh, parathyroid hormonerelated peptide （PTHrP）, protein Patched （Ptch）, Bcl-2 and p21 were detected by RT-PCR. The protein expression levels of Ihh and Ptch were measured by Western blot. MTT assay was used to examine the effects of cyclo on proliferation of PSCs. Apoptosis rate of PSCs was examined by AnnexinV/PI assay of flow cytometric analyses. After PSCs were incubated with cyclo, obvious morphologic changes were observed as compared with the control group. The mRNA expression levels of PTHrP, Ptch and Bcl-2 were decreased to varying degrees in a cyclo dose-dependent manner. However, the expression levels of Ihh and p21 mRNA were increased. The protein expression of Ptch and Ihh had the same change as the mRNA expression. Meanwhile, cyclo could obvi- ously inhibit the proliferation and promote the apoptosis of PSCs. The results indicated that Ihh signaling pathway plays an important role in regulating the proliferation and apoptosis of PSCs, which is probably mediated by Bcl-2 and p21.展开更多
基金Supported by The Japan Society for the Promotion of Science,Kakenhi Grant,No.24390303
文摘Pancreatic cancer is one of the most aggressive and difficult cancers to treat.Despite numerous research efforts,limited success has been achieved in the therapeutic management of patients with this disease.In the current review,we focus on one component of morphogenesis signaling,Hedgehog(Hh),with the aim of developing novel,effective therapies for the treatment of pancreatic cancer.Hh signaling contributes to the induction of a malignant phenotype in pancreatic cancer and is responsible for maintaining pancreatic cancer stem cells.In addition,we propose a novel concept linking Hh signaling and tumor hypoxic conditions,and discuss the effects of Hh inhibitors in clinical trials.The Hh signaling pathway may represent a potential therapeutic target for patients with refractory pancreatic cancer.
基金supported by grants from National Natural Science Foundation of China(81670559)Key Research and Development Project of Shanxi Province(201603D421023)+2 种基金Youth Fund of Shanxi Medical University(02201514)Graduate Student Education Innovation Project of Shanxi(2016BY077)Youth Fund of Ap-plied Basic Research Program of Shanxi(201701D221175)
文摘Background: Previous research suggested that insulin-like growth factor binding protein related protein 1(IGFBPrP1), as a novel mediator, contributes to hepatic fibrogenesis. Matrix metalloproteinases(MMP) and tissue inhibitors of metalloproteinases(TIMP) play an essential role in hepatic fibrogenesis by regulating homeostasis and remodeling of the extracellular matrix(ECM). However, the interaction between IGFBPrP1 and MMP/TIMP is not clear. The present study was to knockdown IGFBPrP1 to investigate the correlation between IGFBPrP1 and MMP/TIMP in hepatic fibrosis. Methods: Hepatic fibrosis was induced by thioacetamide(TAA) in mice. Knockdown of IGFBPrP1 expression by ultrasound-targeted microbubble destruction-mediated CMB-shRNA-IGFBPrP1 delivery, or inhibition of the Hedgehog(Hh) pathway by cyclopamine treatment, was performed in TAA-induced liver fibrosis mice. Hepatic fibrosis was determined by hematoxylin and eosin and Sirius red staining. Hepatic expression of IGFBPrP1, α-smooth muscle actin( α-SMA), transforming growth factor β 1(TGF β1), collagen I, MMPs/TIMPs, Sonic Hedgehog(Shh), and glioblastoma family transcription factors(Gli1) were investigated by immunohistochemical staining and Western blotting analysis. Results: We found that hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I were increased longitudinally in mice with TAA-induced hepatic fibrosis, concomitant with MMP2/TIMP2 and MMP9/TIMP1 imbalance and Hh pathway activation. Knockdown of IGFBPrP1 expression, or inhibition of the Hh pathway, reduced the hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I and re-established MMP2/TIMP2 and MMP9/TIMP1 balance. Conclusions: Our findings suggest that IGFBPrP1 knockdown attenuates liver fibrosis by re-establishing MMP2/TIMP2 and MMP9/TIMP1 balance, concomitant with the inhibition of hepatic stellate cell activation, down-regulation of TGF β1 expression, and degradation of the ECM. Furthermore, the Hh pathway mediates IGFBPrP1 knockdown-induced attenuation of hepatic fibro
基金Coordenação de Aperfeiçoamento de Pessoal de Nível Superior(CAPES,Brazil)Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq,Brazil)。
文摘Colorectal cancer(CRC)represents the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide.The modern concept of cancer biology indicates that cancer is formed of a small population of cells called cancer stem cells(CSCs),which present both pluripotency and self-renewal properties.These cells are considered responsible for the progression of the disease,recurrence and tumor resistance.Interestingly,some cell signaling pathways participate in CRC survival,proliferation,and selfrenewal properties,and most of them are dysregulated in CSCs,including the Wingless(Wnt)/β-catenin,Notch,Hedgehog,nuclear factor kappa B(NF-κB),Janus kinase/signal transducer and activator of transcription(JAK/STAT),peroxisome proliferator-activated receptor(PPAR),phosphatidyl-inositol-3-kinase/Akt/mechanistic target of rapamycin(PI3K/Akt/mTOR),and transforming growth factor-β(TGF-β)/Smad pathways.In this review,we summarize the strategies for eradicating CRC stem cells by modulating these dysregulated pathways,which will contribute to the study of potential therapeutic schemes,combining conventional drugs with CSC-targeting drugs,and allowing better cure rates in anti-CRC therapy.
文摘Background: The PTCH1 gene, also known as Patched 1, is located on the long arm of human chromosome 9 (9q22.3). It encodes the PTCH1 protein, which is a critical transmembrane receptor within the Hedgehog signaling pathway (Hh), playing a pivotal role in cellular communication and developmental processes. Recent studies have highlighted the significance of mutations in PTCH1 in the pathogenesis of lung cancer, positioning it as a crucial molecule for investigation in oncology. Purpose: This review aims to elucidate the role of the PTCH1 and the Hedgehog pathway in the initiation, progression, and potential treatment of lung cancer, thereby providing a theoretical foundation for personalized and precise therapeutic strategies. Method: To ensure a comprehensive review, this study systematically searched for literature related to the PTCH1, lung cancer, and the Hedgehog pathway across multiple databases including PubMed, Web of Science, and CNKI (China National Knowledge Infrastructure). The search strategy involved using specific keywords and advanced filtering options to include the most relevant and recent studies. Initial screening excluded irrelevant articles, followed by a detailed evaluation of the selected studies based on their scientific quality and relevance. Results: This review indicated that specific mutations in the PTCH1 gene are closely associated with the onset and progression of lung cancer. These mutations impede normal Hedgehog signaling, leading to unregulated cell proliferation and tumor growth. Targeting PTCH1, including vismodegib, have shown efficacy in clinical cases, particularly in SCCL with specific PTCH1 mutations, leading to complete remissions. Furthermore, the interaction between PTCH1 and microRNA-212 suggests potential therapeutic approaches by targeting miRNA to regulate PTCH1 expression. In addition, the investigation of traditional Chinese medicines such as Ginsenosides and Cordyceps sinensis extracts has shown their potential to modulate the Hedgehog pathway and reverse drug r
文摘Hedgehog （Hh） signals regulate invertebrate and vertebrate development, yet the role of the pathway in adipose development remains poorly understood. In this report, we found that Hh pathway components are expressed in the fat body of silkworm larvae. Functional analysis of these components in a BmN cell line model revealed that activa- tion of the Hh gene stimulated transcription of Hh pathway components, but inhibited the expression of the adipose marker gene AP2. Conversely, specific RNA interference- mediated knockdown of Hh resulted in increased AP2 expression. This further showed the regulation of Hh signal on the adipose marker gene. In silkworm larval models, enhanced adipocyte differentiation and an increase in adipocyte cell size were observed in silkworms that had been treated with a specific Hh signaling pathway antagonist, cyclopamine. The fat-body-specific Hh blockade tests were consistent with Hh signaling inhibiting silkworm adipogenesis. Our results indicate that the role of Hh signaling in inhibiting fat formation is conserved in vertebrates and invertebrates.
基金Supported by National Natural Science Foundation of China(No.31271516,No.21207084,No.31201072)Research Fund for Doctoral Program of Higher Education of China(No.20111401110011)+1 种基金Oversea Foundation of Shanxi Province(No.20111009,20111010)International S&T Cooperation Program of Shanxi Province~~
文摘Constitutive hedgehog （Hh） signaling is associated with the genesis of medulloblastomas （MB）. The objective of this study is to identify special microRNAs （miRNAs） regulated by the Hh pathway, and to clarify the role of miRNAs during the genesis of MB induced by sustained Hh activation. In the primary screening, we used stemloop RT-PCR to test the expression of 90 different miRNAs in the wildtype （WT） and Ptc-/- MEF cell lines. In the secondary screening, the miRNAs screened from the first screening were validated in the Sufu-/- MEF cell lines. We then verified the expression of miRNAs both in the normal cerebellar tissues and the MB induced by activated Hh pathway, and examined the expression of the other 21 miRNA members of the miR-154 cluster in the MB and normal cerebellum. In the first screening, 13 miRNAs showed significant differential expression in WT and Ptc-/- MEF cell lines, while 10 of them had significant difference in the Sufu-/- MEF cell line. Compared to the normal mouse cerebellum, only 2 miRNAs in 15 miRNAs were differentially expressed between the MB and normal cerebellar tissues. Among 21 members of the miR-154 cluster, 6 miRNAs were downregulated in the MB. Our study demonstrated that miR-154 may be regulated by the Hh pathway, and the activation of the Hh pathway led to the downregulation of the miR-154 cluster, resulting in the genesis of MB.
基金supported by the National Natural Science Foundation of China,No.81330042,81620108018(both to SQF),and 81702147(to ZJW)
文摘Bone marrow-derived mesenchymal stem cells differentiate into neurons under the induction of Schwann cells. However, key microRNAs and related pathways for differentiation remain unclear. This study screened and identified differentially expressed microRNAs in bone marrow- derived mesenchymal stem cells induced by Schwann cell-conditioned medium, and explored targets and related pathways involved in their differentiation into neuronal-like cells. Primary bone marrow-derived mesenchymal stem cells were isolated from femoral and tibial bones, while primary Schwann cells were isolated from bilateral saphenous nerves. Bone marrow-derived mesenchymal stem cells were cultured in unconditioned (control group) and Schwann cell-conditioned medium (bone marrow-derived mesenchymal stem cell + Schwann cell group). Neuronal differentiation of bone marrow-derived mesenchymal stem cells induced by Schwann cell-conditioned medium was observed by time-lapse imaging. Upon induction, the morphology of bone marrow-derived mesencaymal stem cells changed into a neural shape with neurites. Results of quantitative reverse transcription-polymerase chain reaction revealed that nestin mRNA expression was upregulated from 1 to 3 days and downregulated from 3 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. Compared with the control group, microtubule-associated protein 2 mRNA expression gradually increased from 1 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. After 7 days of induction, microRNA analysis iden:ified 83 significantly differentially expressed microRNAs between the two groups. Gene Ontology analysis indicated enrichment of microRNA target genes for neuronal projection development, regulation of axonogenesis, and positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that Hippo, Wnt, transforming growth factor-beta, and Hedgehog signaling pathv/ays were potentially associated with neural differentiation of b
基金supported by a grant from the National Natural Science Foundation of China (No. 30571872).
文摘Summary： The roles of Indian hedgehog （Ihh） signaling pathway in the proliferation and apoptosis of precartilaginous stem cells （PSCs） were investigated. PSCs, labeled with fibroblast growth factor receptor 3 （FGFR-3）, were isolated from neonatal rats by immunomagnetic separation. After identification with FGFR-3 and Col II, the cells were incubated with different concentrations of cyclopamine （cyclo）, the specific inhibitor of Ihh signaling pathway. The morphologic changes of the cells were observed under the inverted phase contrast microscope. The mRNA expression levels of Ihh, parathyroid hormonerelated peptide （PTHrP）, protein Patched （Ptch）, Bcl-2 and p21 were detected by RT-PCR. The protein expression levels of Ihh and Ptch were measured by Western blot. MTT assay was used to examine the effects of cyclo on proliferation of PSCs. Apoptosis rate of PSCs was examined by AnnexinV/PI assay of flow cytometric analyses. After PSCs were incubated with cyclo, obvious morphologic changes were observed as compared with the control group. The mRNA expression levels of PTHrP, Ptch and Bcl-2 were decreased to varying degrees in a cyclo dose-dependent manner. However, the expression levels of Ihh and p21 mRNA were increased. The protein expression of Ptch and Ihh had the same change as the mRNA expression. Meanwhile, cyclo could obvi- ously inhibit the proliferation and promote the apoptosis of PSCs. The results indicated that Ihh signaling pathway plays an important role in regulating the proliferation and apoptosis of PSCs, which is probably mediated by Bcl-2 and p21.
