Prohibitin attenuates oxidative stress and extracellular matrix accumulation in renal interstitial fibrosis disease

PLoS One. 2013 Oct 25;8(10):e77187. doi: 10.1371/journal.pone.0077187. eCollection 2013.

Abstract

Prohibitin is an evolutionary conserved and pleiotropic protein that has been implicated in various cellular functions, including proliferation, tumour suppression, apoptosis, transcription, and mitochondrial protein folding. Both prohibitin over- and under-expression have been implicated in various diseases and cell types. We recently demonstrated that prohibitin down-regulation results in increased renal interstitial fibrosis (RIF). Here we investigated the role of oxidative stress and prohibitin expression in RIF in unilateral ureteral obstructed rats. Lentivirus-based delivery vectors were used to knockdown or over-express prohibitin. Our results show that increased prohibitin expression was negatively correlated with the RIF index, reactive oxygen species, malon dialdehyde, transforming growth factor β1, collagen IV, fibronectin, and cell apoptosis index. In conclusion, we postulate that prohibitin acts as a positive regulator of mechanisms that counteract oxidative stress and extracellular matrix accumulation and therefore has an antioxidative effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Collagen Type IV / genetics
  • Collagen Type IV / metabolism
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology*
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Fibrosis
  • Gene Expression Regulation
  • Genetic Vectors
  • Kidney / metabolism
  • Kidney / pathology*
  • Kidney Diseases / complications
  • Kidney Diseases / genetics*
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Lentivirus / genetics
  • Lentivirus / metabolism
  • Male
  • Malondialdehyde
  • Oxidative Stress
  • Prohibitins
  • Rats
  • Rats, Wistar
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Severity of Illness Index
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Ureteral Obstruction / complications
  • Ureteral Obstruction / genetics*
  • Ureteral Obstruction / metabolism
  • Ureteral Obstruction / pathology

Substances

  • Collagen Type IV
  • Fibronectins
  • Prohibitins
  • Repressor Proteins
  • Transforming Growth Factor beta1
  • Malondialdehyde

Grants and funding

This study was supported by the Nature Science Foundation of China (no. 81060061 and no. 81150017), the Natural Science Foundation of the Guangxi Zhuang Autonomous Region (no. 0832121) and the Health Department of Guangxi Zhuang Autonomous Region (no. 200917), and a Grant for External Collaborative Research AGE-2009 (G.P.C.D.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.