title: Peroxiredoxin 1 inhibits the oxidative stress induced apoptosis in renal tubulointerstitial fibrosis.
abstract: OBJECTIVE
  Apoptosis is one of the most important mechanisms underlying renal tubulointerstitial fibrosis. We identified a role of protein Peroxiredoxin 1 (Prx1) in protecting apoptosis occurred in tubular epithelial cells of the rat and human kidney.
  
  
  METHODS
  Immunohistochemistry (IHC) staining was used to detect Prx1 expression in kidney derived from unilateral-ureteral obstruction (UUO) rats or patients with obstructive nephropathy. Modulation of Prx1 expression by transfecting siRNA and overexpression plasmid approach were carried out in NRK-52E (rat kidney tubular epithelial cell line) cells. UUO-induced apoptosis was determined using TUNEL assay.
  
  
  RESULTS
  Immunohistochemistry staining showed that Prx1 expressed in the cytoplasm of renal tubular epithelial cells, in the kidneys of UUO rats. The reduction was confirmed by both IHC and real-time polymerase chain reaction following a course of renal tubulointerstitial fibrosis in UUO rats and a decrease of Prx1 occurred concomitantly with an elevation of TUNEL-positive cells. Fluorofenidone (AKF-PD), a new anti-tubulointerstitial fibrotic agent, attenuated Prx1 reduction in UUO rats. Furthermore, hydrogen peroxide (H2 O2 )-derived oxidative stress activated p38 MAPK, and induced apoptosis in NRK-52E cells; knockdown of Prx1 sensitized both events in NRK-52E cells, and overexpression of Prx1 diminished the apoptosis and the phosphorylation of p38 CONCLUSION: Downregulation of Prx1 occurred in renal tubular epithelial cells of UUO rats and patients with obstructive nephropathy. Prx1 may alleviate the pathogenesis by inhibiting H2 O2 -induced apoptosis via inhibiting the p38 MAPK pathway. Prx1 may represent a useful target for a protective therapy towards renal tubulointerstitial fibrosis.
authors.affiliation: Division of Nephrology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Mei
authors.affiliation: Division of Nephrology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Zhangzhe
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Division of Nephrology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Lu
authors.affiliation: Division of Nephrology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Division of Pathology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Zhenghao
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Division of Nephrology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Division of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Jishi
authors.initials: J
authors.lastname: Liu
authors.affiliation: Division of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.affiliation: Division of Nephrology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Qiongjing
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Division of Nephrology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Xiangning
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Damu
authors.initials: D
authors.lastname: Tang
authors.affiliation: Division of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Huixiang
authors.initials: H
authors.lastname: Yang
authors.affiliation: Division of Nephrology, Xiangya Hospital, Central South University, Changsha, China.|State Key Laboratory of Medical Genetics of China, Central South University, Changsha, China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Tao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D004195:Disease Models, Animal; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D005260:Female; D005355:Fibrosis; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D007674:Kidney Diseases / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011728:Pyridones / Q000494:pharmacology; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D014517:Ureteral Obstruction / Q000150:complications; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C511655:5-methyl-1-(3-fluorophenyl)-2-(1H)-pyridone; D011728:Pyridones; D006861:Hydrogen Peroxide; C489898:Prdx1 protein, rat; C515940:PRDX1 protein, human; D054464:Peroxiredoxins; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Peroxiredoxin 1; apoptosis; renal tubular epithelial cells; renal tubulointerstitial fibrosis