Authors
Sudaphon Srichan, Pissared Khuituan, Krittee Dejyong, Natapol Duangtum, Julaluk Jiangsakul, Chayada Yoksiri, Nattanun Hautavanija, Sukrit Sangjun, Fittree Hayeeawaema, Warinthorn Chavasiri, Suchada Kaewin, Chatchai Muanprasat, Paradorn Muangnil
Published in
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. Volume 202. Pages 119820. Jul 30, 2026. Epub Jul 30, 2026.
Abstract
Renal fibrosis is the final common pathway of chronic kidney disease and is largely driven by transforming growth factor-β1 (TGF-β1) signaling. TGF-β1 exerts its cellular effects via two main signaling pathways: the canonical Smad-dependent pathway and non-canonical Smad-independent pathways, including MAPK and STAT3 signaling. This study investigated the anti-fibrotic effects of a novel chalcone derivative, DN-053, in vitro and in vivo. In NRK-49F renal fibroblasts, DN-053 dose-dependently inhibited TGF-β1-induced α-smooth muscle actin (α-SMA) expression with an IC50 of 1.13 µM and reduced fibroblast proliferation. DN-053 also attenuated α-SMA expression in established myofibroblasts, suggesting reversibility of activation. Mechanistically, in vitro, DN-053 did not alter Smad3 phosphorylation but significantly suppressed TGF-β1-induced activation of p38 MAPK and STAT3. In a unilateral ureteral obstruction (UUO) mouse model, DN-053 (10 mg/kg/day, i.p.) significantly reduced interstitial collagen deposition and decreased renal expression of collagen I, α-SMA, and TGF-β protein. Collectively, these findings demonstrate that DN-053 exerts potent anti-fibrotic effects in vitro and attenuates renal fibrosis in vivo, supporting further preclinical evaluation of DN-053 as a promising anti-fibrotic lead compound.
PMID:
42531633
Bibliographic data and abstract were imported from PubMed on 31 Jul 2026.
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