Work

Xiebai bining decoction attenuates renal fibrosis in hyperuricemic nephropathy alongside changes in FUNDC1/LC3B autophagy markers and TGF-β1/Smad3 signaling

Year: 2026

Type: article

Abstract: Background Hyperuricemic nephropathy (HN), a major renal complication of hyperuricemia (HUA), is closely associated with renal tubulointerstitial fibrosis. Dysregulated transforming growth factor-β1 (TGF-β1)/Smad3 signaling and impaired mitochondrial quality control may contribute to HN progression. This study evaluated the effects of Xiebai Bining Decoction (XBD) on HN-associated renal fibrosis and examined accompanying changes in FUN14 domain-containing protein 1 (FUNDC1)/LC3B autophagy-related markers and TGF-β1/Smad3 signaling-associated measurements. Methods An HN mouse model was induced by potassium oxonate combined with adenine. Mice were treated with XBD, febuxostat, the autophagy inhibitor 3-methyladenine (3-MA), or XBD plus 3-MA. Serum uric acid (SUA), serum creatinine (Scr), and blood urea nitrogen (BUN) were measured, and renal histopathology and extracellular matrix (ECM) deposition were evaluated. FUNDC1, microtubule-associated protein 1 light chain 3B (LC3B), and TGF-β1/Smad3 signaling-related proteins were examined by Western blotting, immunofluorescence staining, immunohistochemical staining, enzyme-linked immunosorbent assay (ELISA), and transmission electron microscopy. Results XBD reduced SUA, Scr, and BUN levels, improved renal morphology, and alleviated renal tubular injury, ECM deposition, and changes in epithelial and mesenchymal markers in HN mice. XBD treatment was accompanied by higher FUNDC1 and LC3B-related measurements and more TEM-identified autophagosomal profiles; these readouts differed in the 3-MA-treated groups. XBD also decreased TGF-β1 content and downregulated TGF-β receptor type I (TGF-βRI) and phosphorylated Smad3 (p-Smad3) expression. Conclusion XBD treatment was associated with reduced renal injury and fibrosis, changes in FUNDC1- and LC3B-related autophagy markers, and attenuation of TGF-β1/Smad3 pathway-related responses in HN mice. These observations support associations between XBD-related renal protection and autophagy- and fibrosis-associated molecular responses without establishing a direct mechanistic relationship between them.

Source: Frontiers in Cell and Developmental Biology

DOI: 10.3389/fcell.2026.1975823

Authors: Kaiqing Li, Xue Xia, Min Li, Ying Tong

Institutions: Affiliated Hospital of Shaanxi University of Chinese Medicine, Heilongjiang University of Chinese Medicine, First Affiliated Hospital of Heilongjiang University of Chinese Medicine

Language: English

Topic: Gout, Hyperuricemia, Uric Acid

Subfield: Nephrology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801