Photo Credit: Mohammed Haneefa Nizamudeen
The following is a summary of “UHRF1 promotes epithelial-mesenchymal transition mediating renal fibrosis by activating the TGF-β/SMAD signaling pathway,” published in the January 2025 issue of Urology by Yang et al.
Renal fibrosis, a common outcome of chronic kidney diseases, progresses through epithelial-mesenchymal transition (EMT). UHRF1, an epigenetic regulator, may play a key role in its pathogenesis, though the mechanisms remain unclear.
Researchers conducted a retrospective study to explore the role of UHRF1 in renal fibrosis and EMT.
They analyzed data from the GEO and Nephroseq databases, revealing high UHRF1 expression in the unilateral ureteral obstruction (UUO) model and nephropathy patients. Gene set enrichment analysis suggested UHRF1’s involvement in the TGF-β signaling pathway in fibrosis. In vitro, TGF-β1-stimulated HK2 cells were used, and in vivo models of renal fibrosis were induced by UUO and folic acid. UHRF1 knockdown was performed to assess its effect on the TGF-β/SMAD pathway, EMT, and fibrosis. Hinokitiol was applied to evaluate its potential in reducing UHRF1 expression and alleviating fibrosis.
The results showed high UHRF1 expression in both in vitro and in vivo models of renal fibrosis. UHRF1 knockdown inhibited the TGF-β/SMAD signaling pathway, reduced EMT, and attenuated renal fibrosis. Hinokitiol reduced SMAD2/3 phosphorylation and ameliorated EMT and renal fibrosis in both models.
Investigators found that UHRF1 upregulation accelerated EMT and renal fibrosis via the TGF-β/SMAD pathway. Hinokitiol alleviated renal fibrosis by suppressing UHRF1 expression in the kidney.
Source: nature.com/articles/s41598-025-86496-9
