Sirtuin 6 inhibits myofibroblast differentiation via inactivating transforming growth factor‐β1/Smad2 and nuclear factor‐κB signaling pathways in human fetal lung fibroblasts

2018 ◽  
Vol 120 (1) ◽  
pp. 93-104 ◽  
Author(s):  
Qian Zhang ◽  
Wei Tu ◽  
Kunming Tian ◽  
Lianyong Han ◽  
Qin Wang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Fetal Lung ◽  
Nuclear Factor Κb ◽  
Transforming Growth Factor Β1 ◽  
Lung Fibroblasts ◽  
Myofibroblast Differentiation ◽  
Nuclear Factor ◽  
Human Fetal Lung

scholarly journals Pharmacological inhibition of autophagy by 3-MA attenuates hyperuricemic nephropathy

2018 ◽  
Vol 132 (21) ◽  
pp. 2299-2322 ◽  
Author(s):  
Jinfang Bao ◽  
Yingfeng Shi ◽  
Min Tao ◽  
Na Liu ◽  
Shougang Zhuang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Growth Factor Receptor ◽  
Nuclear Factor Κb ◽  
Transforming Growth Factor Β1 ◽  
Renal Tissue ◽  
Tgf Β1

Autophagy has been identified as a cellular process of bulk degradation of cytoplasmic components and its persistent activation is critically involved in the renal damage induced by ureteral obstruction. However, the role and underlying mechanisms of autophagy in hyperuricemic nephropathy (HN) remain unknown. In the present study, we observed that inhibition of autophagy by 3-methyladenine (3-MA) abolished uric acid-induced differentiation of renal fibroblasts to myofibroblasts and activation of transforming growth factor-β1 (TGF-β1), epidermal growth factor receptor (EGFR), and Wnt signaling pathways in cultured renal interstitial fibroblasts. Treatment with 3-MA also abrogated the development of HN in vivo as evidenced by improving renal function, preserving renal tissue architecture, reducing the number of autophagic vacuoles, and decreasing microalbuminuria. Moreover, 3-MA was effective in attenuating renal deposition of extracellular matrix (ECM) proteins and expression of α-smooth muscle actin (α-SMA) and reducing renal epithelial cells arrested at the G2/M phase of cell cycle. Injury to the kidney resulted in increased expression of TGF-β1 and TGFβ receptor I, phosphorylation of Smad3 and TGF-β-activated kinase 1 (TAK1), and activation of multiple cell signaling pathways associated with renal fibrogenesis, including Wnt, Notch, EGFR, and nuclear factor-κB (NF-κB). 3-MA treatment remarkably inhibited all these responses. In addition, 3-MA effectively suppressed infiltration of macrophages and lymphocytes as well as release of multiple profibrogenic cytokines/chemokines in the injured kidney. Collectively, these findings indicate that hyperuricemia-induced autophagy is critically involved in the activation of renal fibroblasts and development of renal fibrosis and suggest that inhibition of autophagy may represent a potential therapeutic strategy for HN.

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