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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 nicotinamide (NIC) on signal transducer and activator of transcription 3 (STAT3) activation and extracellular matrix (ECM) expression in NRK-52E cells. Cells were incubated with NIC at the indicated dose for 48 h. (A) Western blotting visualized the levels of acetyl-STAT3 (Lys685) and phospho-STAT3 (Tyr705). (B) Fibronectin and collagen IV levels were detected by Western blotting. Media containing NIC were changed every 24 h. Data are the mean±SEM of 3–6 experiments. bP<0.05, cP<0.01 compared with control [NIC (0 mmol/L)].
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fig1: Effect of nicotinamide (NIC) on signal transducer and activator of transcription 3 (STAT3) activation and extracellular matrix (ECM) expression in NRK-52E cells. Cells were incubated with NIC at the indicated dose for 48 h. (A) Western blotting visualized the levels of acetyl-STAT3 (Lys685) and phospho-STAT3 (Tyr705). (B) Fibronectin and collagen IV levels were detected by Western blotting. Media containing NIC were changed every 24 h. Data are the mean±SEM of 3–6 experiments. bP<0.05, cP<0.01 compared with control [NIC (0 mmol/L)].

Mentions: Western blot studies showed that nicotinamide, an inhibitor of SIRTs35,36, significantly enhanced STAT3 acetylation on Lys685 and the phosphorylation on Tyr705 in NRK-52E cells (48 h) (Figure 1A). These effects were accompanied by an accumulation of fibronectin and collagen IV (Figure 1B).


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 nicotinamide (NIC) on signal transducer and activator of transcription 3 (STAT3) activation and extracellular matrix (ECM) expression in NRK-52E cells. Cells were incubated with NIC at the indicated dose for 48 h. (A) Western blotting visualized the levels of acetyl-STAT3 (Lys685) and phospho-STAT3 (Tyr705). (B) Fibronectin and collagen IV levels were detected by Western blotting. Media containing NIC were changed every 24 h. Data are the mean±SEM of 3–6 experiments. bP<0.05, cP<0.01 compared with control [NIC (0 mmol/L)].
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Effect of nicotinamide (NIC) on signal transducer and activator of transcription 3 (STAT3) activation and extracellular matrix (ECM) expression in NRK-52E cells. Cells were incubated with NIC at the indicated dose for 48 h. (A) Western blotting visualized the levels of acetyl-STAT3 (Lys685) and phospho-STAT3 (Tyr705). (B) Fibronectin and collagen IV levels were detected by Western blotting. Media containing NIC were changed every 24 h. Data are the mean±SEM of 3–6 experiments. bP<0.05, cP<0.01 compared with control [NIC (0 mmol/L)].
Mentions: Western blot studies showed that nicotinamide, an inhibitor of SIRTs35,36, significantly enhanced STAT3 acetylation on Lys685 and the phosphorylation on Tyr705 in NRK-52E cells (48 h) (Figure 1A). These effects were accompanied by an accumulation of fibronectin and collagen IV (Figure 1B).

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