MFAP4 deficiency alleviates renal fibrosis through inhibition of NF‐κB and TGF‐β/Smad signaling pathways

mice exhibited attenuated nuclear translocation of p65 (the hub subunit of nuclear factor (NF)-κB signaling pathway), suppressed activation of transforming growth factor (TGF)-β/Smad pathways, and downregulated expression of fibronectin, collagen I, and plasminogen activator inhibitor-1. The knockdown of MFAP4 mitigated the TGF-β-induced upregulated expression of fibronectin, collagen I, and plasminogen activator inhibitor-1 in the human proximal tubular epithelial cells (HK-2). Compared to the HK-2 cells transfected with sh-MFAP4, the HK-2 cells co-transfected with sh-MFAP4 and Ad-MFAP4 exhibited severe inflammatory response and increased fibrosis-related proteins expression. Mechanistically, the knockdown of MFAP4 inhibited the activation of NF-κB and TGF-β/Smad signaling pathways and downregulated the expression of fibrosis-related proteins. The findings of this study indicate that MFAP4 is involved in UUO-induced renal fibrosis through regulation of NF-κB and TGF-β/Smad pathways.