Hyaluronan and proteoglycan link protein 1(Hapln1)supports active cardiomyogenesis in zebrafish hearts,but its regulation in mammal cardiomyocytes is unclear.This study aimed to explore the potential regulation of Hap...Hyaluronan and proteoglycan link protein 1(Hapln1)supports active cardiomyogenesis in zebrafish hearts,but its regulation in mammal cardiomyocytes is unclear.This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell(hiPSC)-derived cardiomyocytes(CMs)and an adult mouse model of myocardial infarction.HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models,respectively.Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration.The results showed that recombinant human Hapln1(rhHapln1)promotes the proliferation of hiPSC-CMs in a dose-dependent manner.As a physical binding protein of Hapln1,versican interacted with Nodal growth differentiation factor(NODAL)and growth differentiation factor 11(GDF11).GDF11,but not NODAL,was expressed by hiPSC-CMs.GDF11 expression was unaffected by rhHapln1 treatment.However,this molecule was required for rhHapln1-mediated activation of the transforming growth factor(TGF)-β/Drosophila mothers against decapentaplegic protein(SMAD)2/3 signaling in hiPSC-CMs,which stimulates cell dedifferentiation and proliferation.Recombinant mouse Hapln1(rmHapln1)could induce cardiac regeneration in the adult mouse model of myocardial infarction.In addition,rmHapln1 induced hiPSC-CM proliferation.In conclusion,Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-β/SMAD2/3 signaling pathway.Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a potential reagent for repairing damaged hearts.展开更多
The lumbar spine,an important part of the body’s motor mechanism,is more susceptible to damage as it bears most of the body’s load.Age can cause clinical manifestations such as neurological impairment,back and leg p...The lumbar spine,an important part of the body’s motor mechanism,is more susceptible to damage as it bears most of the body’s load.Age can cause clinical manifestations such as neurological impairment,back and leg pain in the lumbar spine.External forces result in nucleus pulposus out,destruction of the intervertebral disc fibrous ring,and gradual aging and damage.Lumbar degenerative change is a common middle-aged and old-aged disease,and its clinical symptoms on the initial stage are not obvious,but it becomes more and more serious as they get older.Patients with severe lumbar degenerative changes will appear symptoms such as urinary and fecal incontinence,lower extremity numbness,back pain,and sexual dysfunction.The main reason for back pain and leg pain is the degenerative changes in the lumbar intervertebral discs,at the same time which also leads to patients’lumbar instability.This study focuses on the correlation analysis of intervertebral disc degeneration with HTRA1 and HAPLN1 gene polymorphisms.展开更多
基金Shaanxi Province Natural Science Foundation,China(Grant No.:2021JM-568).
文摘Hyaluronan and proteoglycan link protein 1(Hapln1)supports active cardiomyogenesis in zebrafish hearts,but its regulation in mammal cardiomyocytes is unclear.This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell(hiPSC)-derived cardiomyocytes(CMs)and an adult mouse model of myocardial infarction.HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models,respectively.Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration.The results showed that recombinant human Hapln1(rhHapln1)promotes the proliferation of hiPSC-CMs in a dose-dependent manner.As a physical binding protein of Hapln1,versican interacted with Nodal growth differentiation factor(NODAL)and growth differentiation factor 11(GDF11).GDF11,but not NODAL,was expressed by hiPSC-CMs.GDF11 expression was unaffected by rhHapln1 treatment.However,this molecule was required for rhHapln1-mediated activation of the transforming growth factor(TGF)-β/Drosophila mothers against decapentaplegic protein(SMAD)2/3 signaling in hiPSC-CMs,which stimulates cell dedifferentiation and proliferation.Recombinant mouse Hapln1(rmHapln1)could induce cardiac regeneration in the adult mouse model of myocardial infarction.In addition,rmHapln1 induced hiPSC-CM proliferation.In conclusion,Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-β/SMAD2/3 signaling pathway.Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a potential reagent for repairing damaged hearts.
基金This work was supported by the Project of the Department of Science and Technology in Shaanxi Province(2020JM-702).
文摘The lumbar spine,an important part of the body’s motor mechanism,is more susceptible to damage as it bears most of the body’s load.Age can cause clinical manifestations such as neurological impairment,back and leg pain in the lumbar spine.External forces result in nucleus pulposus out,destruction of the intervertebral disc fibrous ring,and gradual aging and damage.Lumbar degenerative change is a common middle-aged and old-aged disease,and its clinical symptoms on the initial stage are not obvious,but it becomes more and more serious as they get older.Patients with severe lumbar degenerative changes will appear symptoms such as urinary and fecal incontinence,lower extremity numbness,back pain,and sexual dysfunction.The main reason for back pain and leg pain is the degenerative changes in the lumbar intervertebral discs,at the same time which also leads to patients’lumbar instability.This study focuses on the correlation analysis of intervertebral disc degeneration with HTRA1 and HAPLN1 gene polymorphisms.
