title: PTPRO-associated hepatic stellate cell activation plays a critical role in liver fibrosis.
abstract: OBJECTIVE
  PTPRO (protein tyrosine phosphatase, receptor type O) is implicated in diverse physiological and pathological processes in cancer and hepatic ischemia/reperfusion injury, although little is known about its role in hepatic fibrosis.
  
  
  METHODS
  Here, by using genetically deficient mice, we reported that PTPRO knockout (PTPRO(-/-)) significantly attenuated liver injury, release of inflammatory factors, tissue remodeling, and liver fibrosis in two experimental mouse models of fibrogenesis induced by bile-duct ligation or carbon tetrachloride administration.
  
  
  RESULTS
  However, we proved that PTPRO expression was strongly downregulated in clinical and experimental liver fibrosis specimens. Further investigations revealed that stimulation of primary hepatic stellate cells (HSCs) and hepatocytes with specific activator platelet-derived growth factor (PDGF)-BB increased PTPRO transcription in HSCs but had the opposite effect in primary hepatocytes. More importantly, synthetic short hairpin RNA targeting PTPRO significantly neutralized PDGF-BB-induced HSC proliferation and myofibroblast marker expression through downregulated phosphorylation of extracellular signal-regulated kinase (ERK) and AKT.
  
  
  CONCLUSIONS
  These observations confirm that PTPRO plays a critical role in liver fibrogenesis by affecting PDGF signaling in HSC activation and might be developed into a feasible therapeutic approach for the treatment of chronic fibrotic liver diseases.
authors: Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, P.R. China.
authors: Xudong
authors: X
authors: Zhang
authors: Zhongming
authors: Z
authors: Tan
authors: Youjing
authors: Y
authors: Wang
authors: Junwei
authors: J
authors: Tang
authors: Runjiu
authors: R
authors: Jiang
authors: Jiajie
authors: J
authors: Hou
authors: Han
authors: H
authors: Zhuo
authors: Xiaochen
authors: X
authors: Wang
authors: Jie
authors: J
authors: Ji
authors: Xihu
authors: X
authors: Qin
authors: Beicheng
authors: B
authors: Sun
mesh_terms: D000818:Animals; D000077214:Becaplermin; D002251:Carbon Tetrachloride / Q000633:toxicity; D049109:Cell Proliferation / Q000235:genetics*; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D020574:Proto-Oncogene Proteins c-sis / Q000008:administration & dosage / Q000378:metabolism*; D034741:RNA, Small Interfering; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D034741:RNA, Small Interfering; D000077214:Becaplermin; D002251:Carbon Tetrachloride; C516890:Ptpro protein, mouse; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3