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Inhibition of STAT3 acetylation is associated with angiotesin renal fibrosis in the obstructed kidney.

Ni J, Shen Y, Wang Z, Shao DC, Liu J, Fu LJ, Kong YL, Zhou L, Xue H, Huang Y, Zhang W, Yu C, Lu LM - Acta Pharmacol. Sin. (2014)

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.

ABSTRACT

Aim: 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).

Conclusion: STAT3 acetylation plays an important role in activation of STAT3 signaling pathway and consequent renal fibrosis.

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Related in: MedlinePlus

Effect of Res on UUO-induced STAT3 activation and expression of pro-fibrotic genes in the obstructed kidney. Control and UUO mice received vehicle or 100 mg/kg Res by oral gavage once a day for 1 d (A) or 3 d (B). (A) Acetyl-STAT3 (Lys685) and phospho-STAT3 (Tyr705) were analyzed by Western blot analysis. (B) Fibronectin, collagen IV, α-SMA, and collagen I were analyzed by Western blot analysis. Data are the mean±SEM of 4 animals. cP<0.01 compared with vehicle (Veh). fP<0.01 compared with UUO with vehicle (UUO+Veh).
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fig5: Effect of Res on UUO-induced STAT3 activation and expression of pro-fibrotic genes in the obstructed kidney. Control and UUO mice received vehicle or 100 mg/kg Res by oral gavage once a day for 1 d (A) or 3 d (B). (A) Acetyl-STAT3 (Lys685) and phospho-STAT3 (Tyr705) were analyzed by Western blot analysis. (B) Fibronectin, collagen IV, α-SMA, and collagen I were analyzed by Western blot analysis. Data are the mean±SEM of 4 animals. cP<0.01 compared with vehicle (Veh). fP<0.01 compared with UUO with vehicle (UUO+Veh).

Mentions: Resveratrol treatment of UUO mice through gavage decreased STAT3 acetylation on Lys685 (Figure 5A). This effect was accompanied by a reduction in UUO-induced Tyr705 phosphorylation (1 d) (Figure 5A). Resveratrol also inhibited UUO-induced upregulation of fibronectin, collagen I, collagen IV, and α-SMA protein levels in the obstructed kidney (3 d) (Figure 5B).


Inhibition of STAT3 acetylation is associated with angiotesin renal fibrosis in the obstructed kidney.

Ni J, Shen Y, Wang Z, Shao DC, Liu J, Fu LJ, Kong YL, Zhou L, Xue H, Huang Y, Zhang W, Yu C, Lu LM - Acta Pharmacol. Sin. (2014)

Effect of Res on UUO-induced STAT3 activation and expression of pro-fibrotic genes in the obstructed kidney. Control and UUO mice received vehicle or 100 mg/kg Res by oral gavage once a day for 1 d (A) or 3 d (B). (A) Acetyl-STAT3 (Lys685) and phospho-STAT3 (Tyr705) were analyzed by Western blot analysis. (B) Fibronectin, collagen IV, α-SMA, and collagen I were analyzed by Western blot analysis. Data are the mean±SEM of 4 animals. cP<0.01 compared with vehicle (Veh). fP<0.01 compared with UUO with vehicle (UUO+Veh).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4125712&req=5

fig5: Effect of Res on UUO-induced STAT3 activation and expression of pro-fibrotic genes in the obstructed kidney. Control and UUO mice received vehicle or 100 mg/kg Res by oral gavage once a day for 1 d (A) or 3 d (B). (A) Acetyl-STAT3 (Lys685) and phospho-STAT3 (Tyr705) were analyzed by Western blot analysis. (B) Fibronectin, collagen IV, α-SMA, and collagen I were analyzed by Western blot analysis. Data are the mean±SEM of 4 animals. cP<0.01 compared with vehicle (Veh). fP<0.01 compared with UUO with vehicle (UUO+Veh).
Mentions: Resveratrol treatment of UUO mice through gavage decreased STAT3 acetylation on Lys685 (Figure 5A). This effect was accompanied by a reduction in UUO-induced Tyr705 phosphorylation (1 d) (Figure 5A). Resveratrol also inhibited UUO-induced upregulation of fibronectin, collagen I, collagen IV, and α-SMA protein levels in the obstructed kidney (3 d) (Figure 5B).

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.

ABSTRACT

Aim: 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).

Conclusion: STAT3 acetylation plays an important role in activation of STAT3 signaling pathway and consequent renal fibrosis.

Show MeSH
Related in: MedlinePlus