Increased HA/CD44/TGFβ signaling implicates in renal fibrosis of a Col4a5 mutant Alport mice

• DOI: 10.1186/s10020-025-01146-0
• Publication Date: 2025-03-12T17:35:57Z
• Authors: Yantao Bao; Weiqing Wu; Jiyun Lin; Yuankai Yang; Sheng Lin; Jindi Su; Yueyuan Qin; Baojiang Wang; Shan Duan
• Keywords: Alport syndrome; HEK 293 cells

Abstract X-linked Alport syndrome (XLAS) caused by COL4A5 gene mutation is a hereditary disease that affects mainly the kidney. XLAS patients, especially males whose single copy of disrupted, suffer from life-threatening renal disease, mechanism which remains unclear. Renal fibrosis characteristic pathology observed in kidney tissue. However, molecular path loss-of-function to fibrotic largely unknown. On basis previously established mouse model, our study revealed an activated CD44-TGFβ signaling known strongly promote fibrosis, along with increased level low weight hyaluronan (LMW-HA) instead high (HMW-HA), activate CD44-dependent TGFβ tissues. Additionally, synthase 2 (HAS2), enzyme primarily responsible for HA production, was found be upregulated XLAS. In particular, vitro studies knockdown human kidney-derived HEK-293 cells can upregulate HAS2 at both RNA and protein levels. The novel contribution finding deficiency may lead overexpression accumulation signaling, thereby promoting possibly suggesting CD44 are potential therapeutic targets impeding