title: Role of TGF-β1/p38 MAPK pathway in hepatitis B virus-induced tubular epithelial-myofibroblast transdifferentiation.
abstract: OBJECTIVE
  This study is to investigate the hepatitis B virus (HBV)-induced tubular epithelial-myofibroblast transdifferentiation (TEMT) in human renal tubular epithelial HK-2 cells.
  
  
  METHODS
  Human proximal tubular epithelial HK-2 cells were cultured. These HK-2 cells were divided into 4 groups: the blank control group, the vector control group, the HBV-transfected group, and the inhibitor-treated group. Transfection was performed with lipofectamine. Measurements of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) in culture supernatant were determined by electrochemiluminescence immunoassay. Immunocytochemical staining, reverse transcription PCR (RT-PCR), and Western blot analysis were performed to detect the mRNA and protein expression levels, respectively.
  
  
  RESULTS
  The immunocytochemical staining showed that, the expression level of E-cadherin was dramatically decreased, while the α-SMA expression level was significantly elevated, in HBV-transfected HK-2 cells. The mRNA level of TGF-β1 and the protein level of p-p38 mitogen-activated protein kinase (MAPK) were elevated in HK-2 cells transfected with HBV. When treated with the p38 MAPK-specific inhibitor, the activation of p38 MAPK was eliminated in HBV-transfected HK-2 cells. In addition, the altered expression levels of E-cadherin and α-SMA, the increased contents of HBeAg and HBsAg in the culture supernatant, as well as the morphological changes of TEMT in HBV-transfected HK-2 cells, were all reversed by the inhibiter treatment.
  
  
  CONCLUSIONS
  HBV transfection could induce TEMT in HK-2 cells, which was mediated by the TGF-β1/p38 MAPK pathway. These findings provide new insights into the prevention and treatment of HBV-associated glomerulonephritis.
authors.affiliation: Department of Gastroenterology, Qianfoshan Hospital Affiliated to Shandong University Jinan 250014, Shandong, China.
authors.forename: Changhong
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, Qilu Hospital of Shandong University Jinan 250012, Shandong, China.
authors.forename: Fengzhe
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Preventive Medicine, Shandong University of Traditional Chinese Medicine Jinan 250013, Shandong, China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Han
authors.affiliation: School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences Jinan 250062, Shandong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Qianfoshan Hospital Affiliated to Shandong University Jinan 250014, Shandong, China.
authors.forename: Yiguo
authors.initials: Y
authors.lastname: Wang
mesh_terms: D002460:Cell Line; D054338:Cell Transdifferentiation / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D006515:Hepatitis B virus; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism* / Q000821:virology; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D015398:Signal Transduction / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D053773:Transforming Growth Factor beta1; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Hepatitis B virus (HBV); TGF-β1/p38 MAPK pathway; human tubular epithelial cells; tubular epithelial-myofibroblast transdifferentiation (TEMT)