title: Activated effects of parathyroid hormone-related protein on human hepatic stellate cells.
abstract: OBJECTIVE
  After years of experiments and clinical studies, parathyroid hormone-related protein(PTHrP) has been shown to be a bone formation promoter that elicits rapid effects with limited adverse reaction. Recently, PTHrP was reported to promote fibrosis in rat kidney in conjunction with transforming growth factor-beta1 (TGF-β1), which is also a fibrosis promoter in liver. However, the effect of PTHrP in liver has not been determined. In this study, the promoting actions of PTHrP were first investigated in human normal hepatic stellate cells (HSC) and LX-2 cell lines.
  
  
  METHODS
  TGF-β1, alpha-smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP-2), and collagen I mRNA were quantified by real-time polymerase chain reaction (PCR) after HSCs or LX-2 cells were treated with PTHrP(1-36) or TGF-β1. Protein levels were also assessed by western-blot analysis. Alpha-SMA were also detected by immunofluorescence, and TGF-β1 secretion was measured with enzyme-linked immunosorbent assay (ELISA) of HSC cell culture media.
  
  
  RESULTS
  In cultured human HSCs, mRNA and protein levels of α-SMA, collagen I, MMP-2, and TGF-β1 were increased by PTHrP treatment. A similar increasing pattern was also observed in LX-2 cells. Moreover, PTHrP significantly increased TGF-β1 secretion in cultured media from HSCs.
  
  
  CONCLUSIONS
  PTHrP activated HSCs and promoted the fibrosis process in LX-2 cells. These procedures were probably mediated via TGF-β1, highlighting the potential effects of PTHrP in the liver.
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
authors.forename: Fen-Fen
authors.initials: FF
authors.lastname: Liang
authors.forename: Cui-Ping
authors.initials: CP
authors.lastname: Liu
authors.forename: Li-Xuan
authors.initials: LX
authors.lastname: Li
authors.forename: Min-Min
authors.initials: MM
authors.lastname: Xue
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.forename: Yu
authors.initials: Y
authors.lastname: Guo
authors.forename: Lan
authors.initials: L
authors.lastname: Bai
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009130:Muscle, Smooth / Q000737:chemistry; D044162:Parathyroid Hormone-Related Protein / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000199:Actins; D024042:Collagen Type I; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D053773:Transforming Growth Factor beta1; D020778:Matrix Metalloproteinase 2