title: Gja1acts downstream ofAcvr1to regulate uterine decidualization viaHand2in mice.
abstract: AlthoughGja1has been proved to play an important role in uterine decidualization, its regulatory mechanism remains largely unknown. Here, we showed thatGja1was highly expressed in the decidual cells and promoted the proliferation of uterine stromal cells and expression ofPrl8a2andPrl3c1, which were two well-known differentiation markers for decidualization. Further analysis revealed thatGja1might act downstream ofAcvr1and cAMP to regulate the differentiation of uterine stromal cells. Administration of cAMP analog 8-Br-cAMP toAcvr1siRNA-transfected stromal cells resulted in an obvious increase ofGja1expression, whereas PKA inhibitor H89 impeded the induction ofGja1elicited byAcvr1overexpression, indicating that cAMP-PKA signal mediates the regulation ofAcvr1onGja1expression. In uterine stromal cells, knockdown ofGja1blocked the cAMP induction ofHand2Moreover, siRNA-mediated downregulation ofHand2impaired the stimulatory effects ofGja1overexpression on the expression ofPrl8a2andPrl3c1, whereas constitutive expression ofHand2reversed the inhibitory effects ofGja1siRNA on stromal differentiation. Meanwhile,Gja1might play a vital role in the crosstalk betweenAcvr1andHand2Collectively,Gja1may act downstream of cAMP-PKA signal to mediate the effects ofAcvr1on the differentiation of uterine stromal cells through targetingHand2.
authors.affiliation: College of Veterinary MedicineJilin University, Changchun, People's Republic of China.
authors.forename: Hai-Fan
authors.initials: HF
authors.lastname: Yu
authors.affiliation: College of Veterinary MedicineJilin University, Changchun, People's Republic of China.
authors.forename: Zhan-Peng
authors.initials: ZP
authors.lastname: Yue
authors.affiliation: College of Veterinary MedicineJilin University, Changchun, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: College of Veterinary MedicineJilin University, Changchun, People's Republic of China.
authors.forename: Zhan-Qing
authors.initials: ZQ
authors.lastname: Yang
authors.affiliation: College of Veterinary MedicineJilin University, Changchun, People's Republic of China.
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Zhang
authors.affiliation: College of Veterinary MedicineJilin University, Changchun, People's Republic of China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Geng
authors.affiliation: College of Veterinary MedicineJilin University, Changchun, People's Republic of China guobin79@jlu.edu.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Guo
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000502:physiology; D014599:Uterus / Q000502:physiology*
chemical_list: D030201:Activin Receptors, Type I; D051792:Basic Helix-Loop-Helix Proteins; D018031:Connexin 43; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D012333:RNA, Messenger; C543076:GJA1 protein, mouse; C498766:Hand2 protein, mouse; C498943:Acvr1 protein, mouse
keywords: Acvr1; Gja1; Hand2; decidualization; uterine stromal cell