title: RSPOs facilitated HSC activation and promoted hepatic fibrogenesis.
abstract: Roof plate-specific spondin (RSPO) proteins are potent Wnt pathway agonists and involve in a broad range of developmental and physiological processes. This study investigated the activities and mechanisms of RSPOs in liver fibrogenesis, especially in hepatic stellate cell (HSC) activation. HSC activation was assessed by fibrosis biomarker (α-smooth muscle actin and Collagen-I), phenotypic change (accumulation of lipid droplets), and increased proliferation. Similarly, Wnt pathway activity was evaluated by the expression of nuclear β-catenin and T cell-specific transcription factors (TCF) activity. We found RSPOs were overexpressed in human fibrotic liver tissue and the expressions were correlated with liver fibrosis stages. In vitro studies showed RSPOs level increased during HSC activation, and stimuli with RSPOs enhanced Wnt pathway activity and promoted HSC activation subsequently. Furthermore, in vivo experiments demonstrated that the knockdown of RSPOs suppressed both Wnt pathway activity and HSC activation. Interestingly, the inhibitor of the Wnt signaling pathway Dickkopf1 impairs RSPOs effects on HSCs. Taken together, our results revealed that RSPOs facilitated HSC activation and promote liver fibrogenesis by enhancing the Wnt pathway.
authors: Centre for Gastroenterology and Hepatology, The Maternity and Child Health Care Hospital affiliated to Jiaxing College, Jiaxing, 314001, Zhejiang Province, PR China.|Centre for Gastroenterology and Hepatology, The First Affiliated Hospital of Jiaxing College, Jiaxing, 314001, Zhejiang Province, PR China.
authors: Xinguang
authors: X
authors: Yin
authors: Intensive Care Unit, The Second Affiliated Hospital of Zhejiang University, Hangzhou, 310009, Zhejiang Province, PR China.
authors: Huixing
authors: H
authors: Yi
authors: Department of Basic Medicine Sciences, School of Medicine, Zhejiang University, Hangzhou, 310058, China.
authors: Linlin
authors: L
authors: Wang
authors: Deparment of Pathology, The First Affiliated Hospital of Jiaxing College, Jiaxing, 314001, Zhejiang Province, PR China.
authors: Wanxin
authors: W
authors: Wu
authors: Centre for Gastroenterology and Hepatology, The First Affiliated Hospital of Jiaxing College, Jiaxing, 314001, Zhejiang Province, PR China.
authors: Xiaojun
authors: X
authors: Wu
authors: Centre for Gastroenterology and Hepatology, The First Affiliated Hospital of Jiaxing College, Jiaxing, 314001, Zhejiang Province, PR China.
authors: Linghua
authors: L
authors: Yu
mesh_terms: D000368:Aged; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D018920:Coculture Techniques; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D055166:Hepatic Stellate Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D015398:Signal Transduction; D019699:Thrombospondins / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin; D000098907:R-Spondins
chemical_list: D024042:Collagen Type I; D036341:Intercellular Signaling Peptides and Proteins; D019699:Thrombospondins; D051153:Wnt Proteins; D051176:beta Catenin; C495270:CTNNB1 protein, human; C501126:DKK1 protein, human; C503243:RSPO1 protein, human; D000098907:R-Spondins; C475438:RSPO3 protein, human; C557408:Rspo2 protein, human
keywords: HSC; RSPO; Wnt pathway; hepatic fibrosis