title: Inhibition of STAT3 acetylation is associated with angiotesin renal fibrosis in the obstructed kidney.
abstract: OBJECTIVE
  To explore the relationship between the signal transducer and activator of transcription 3 (STAT3) signaling and renal fibrosis.
  
  
  METHODS
  Rat renal tubular epithelial NRK-52E cells were treated with angiotesin II (Ang II), nicotinamide (an inhibitor of NAD+-dependent class III protein deacetylases, SIRT1-7), or resveratrol (an activator of SIRT1). Mice underwent unilateral ureteral obstruction (UUO) were used for in vivo studies. Renal interstitial fibrosis was observed with HE and Masson's trichrome staining. STAT3 acetylation and phosphorylation, fibronectin, collagen I, collagen IV, and α-smooth muscle actin (α-SMA) levels were examined using Western blotting.
  
  
  RESULTS
  Nicotinamide (0.625-10 mmol/L) dose-dependently increased STAT3 acetylation on Lys685 and phosphorylation on Tyr705 in NRK-52E cells, accompanied by accumulation of fibronectin and collagen IV. Ang II increased STAT3 phosphorylation on Tyr705 and the expression of fibronectin, collagen IV and α-SMA in the cells. Pretreatment with resveratrol (12.5 μmol/L) blocked Ang II-induced effects in the cells. UUO induced marked STAT3 phosphorylation, fibronectin, collagen IV and α-SMA accumulation, and renal interstitial fibrosis in the obstructed kidneys, which were significantly attenuated by daily administration of resveratrol (100 mg/kg).
  
  
  CONCLUSIONS
  STAT3 acetylation plays an important role in activation of STAT3 signaling pathway and consequent renal fibrosis.
authors: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors: Jun
authors: J
authors: Ni
authors: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors: Yang
authors: Y
authors: Shen
authors: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors: Zhen
authors: Z
authors: Wang
authors: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors: De-cui
authors: DC
authors: Shao
authors: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors: Jia
authors: J
authors: Liu
authors: Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors: Lan-jun
authors: LJ
authors: Fu
authors: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors: Ya-li
authors: YL
authors: Kong
authors: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors: Li
authors: L
authors: Zhou
authors: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors: Hong
authors: H
authors: Xue
authors: School of Biomedical Sciences and Institute of Vascular Medicine, Chinese University of Hong Kong, Hong Kong, China.
authors: Yu
authors: Y
authors: Huang
authors: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors: Wei
authors: W
authors: Zhang
authors: Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors: Chen
authors: C
authors: Yu
authors: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors: Li-min
authors: LM
authors: Lu
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000804:Angiotensin II / Q000276:immunology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D002460:Cell Line; D005355:Fibrosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007674:Kidney Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D051381:Rats; D000077185:Resveratrol; D050796:STAT3 Transcription Factor / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D050796:STAT3 Transcription Factor; D013267:Stilbenes; D000804:Angiotensin II; D000077185:Resveratrol