Pharmacological inhibition of autophagy by 3-MA attenuates hyperuricemic nephropathy

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