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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

Unilateral ureteral obstruction (UUO) induced pro-fibrotic responses in the kidney. (A) Acetyl-STAT3 (Lys685) and phospho-STAT3 (Tyr705) were analyzed by Western blot analysis after UUO for 1 d. (B) Western blotting visualized fibronectin, collagen IV and α-SMA in a sample time course of UUO mice. Data are the mean±SEM of 6 animals. bP<0.05 compared with sham.
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fig4: Unilateral ureteral obstruction (UUO) induced pro-fibrotic responses in the kidney. (A) Acetyl-STAT3 (Lys685) and phospho-STAT3 (Tyr705) were analyzed by Western blot analysis after UUO for 1 d. (B) Western blotting visualized fibronectin, collagen IV and α-SMA in a sample time course of UUO mice. Data are the mean±SEM of 6 animals. bP<0.05 compared with sham.

Mentions: In UUO mice, a significant increase in STAT3 phosphorylation on Tyr705 was observed 1 d after surgery, whereas no obvious change in STAT3 acetylation on Lys685 was found (Figure 4A). The fibrotic associated proteins, including fibronectin, collagen IV and α-SMA, and collagen I were increased in UUO mice and showed statistical significance starting on the third day after surgery (Figure 4B).


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)

Unilateral ureteral obstruction (UUO) induced pro-fibrotic responses in the kidney. (A) Acetyl-STAT3 (Lys685) and phospho-STAT3 (Tyr705) were analyzed by Western blot analysis after UUO for 1 d. (B) Western blotting visualized fibronectin, collagen IV and α-SMA in a sample time course of UUO mice. Data are the mean±SEM of 6 animals. bP<0.05 compared with sham.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: Unilateral ureteral obstruction (UUO) induced pro-fibrotic responses in the kidney. (A) Acetyl-STAT3 (Lys685) and phospho-STAT3 (Tyr705) were analyzed by Western blot analysis after UUO for 1 d. (B) Western blotting visualized fibronectin, collagen IV and α-SMA in a sample time course of UUO mice. Data are the mean±SEM of 6 animals. bP<0.05 compared with sham.
Mentions: In UUO mice, a significant increase in STAT3 phosphorylation on Tyr705 was observed 1 d after surgery, whereas no obvious change in STAT3 acetylation on Lys685 was found (Figure 4A). The fibrotic associated proteins, including fibronectin, collagen IV and α-SMA, and collagen I were increased in UUO mice and showed statistical significance starting on the third day after surgery (Figure 4B).

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