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The endothelial cells lining these aberrant neovessels exhibit abnormal morphology, with loosely attached or absent pericytes and the basement membrane (BM) is often disrupted. Advanced glycation end products (AGEs) promote pathological angiogenesis in diabetic vascular complications, but whether the vascular BM structure is altered and the underlying molecular mechanisms remain unclear. By analysing single\u2010cell RNA sequencing data (GSE204880) from the oxygen\u2010induced retinopathy mouse model, this study found heterogeneous expression of type IV collagen (Col\u2010IV) and laminin in endothelial cells, with enrichment of the AGE\u2010RAGE pathway and BM\u2010related pathways. Experimental results demonstrated that AGEs induce abnormal distribution of Col\u2010IV in vascular BM, along with increased Col\u2010IV levels in mouse serum and endothelial\u2010pericyte co\u2010culture supernatants, suggesting excessive BM degradation. Additionally, AGEs upregulated CD44 and matrix metalloproteinases 9 (MMP9)\u00a0protein levels in retinal tissues and endothelial cells. Knockout\/knockdown of CD44 or inhibition of MMP9, can both significantly alleviate BM structural disruption and abnormal angiogenesis. The down\u2010regulation of CD44 expression or application of \u03b3\u2010secretase inhibitor DAPT attenuated AGEs\u2010promoted MMP9 expression and secretion. Moreover, AGEs facilitated \u03b2\u2010catenin nuclear translocation and its interaction with TCF4. When this interaction was blocked by LF3, AGEs\u2010induced CD44 upregulation was reduced, and pathological angiogenesis and BM abnormalities were partially restored. These findings suggest that AGEs upregulate endothelial CD44 expression via \u03b2\u2010catenin\/TCF4 signalling pathway, which in turn promotes MMP9\u2010mediated excessive degradation of BM components, leading to structural disorganisation and impaired vascular maturation in pathological angiogenesis.<\/jats:p>","DOI":"10.1111\/jcmm.71088","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T04:41:11Z","timestamp":1773722471000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Increased CD44 Expression in Endothelial Cells Induced by Advanced Glycation End Products Leads to Insufficient Maturation of Angiogenesis"],"prefix":"10.1111","volume":"30","author":[{"given":"Xiaoxia","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pathophysiology School of Basic Medical Sciences, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuanhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology School of Basic Medical Sciences, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqing","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology School of Basic Medical Sciences, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology School of Basic Medical Sciences, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenfeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology School of Basic Medical Sciences, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tairan","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology School of Basic Medical Sciences, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology School of Basic Medical Sciences, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruimin","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology School of Basic Medical Sciences, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology School of Basic Medical Sciences, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology School of Basic Medical Sciences, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8931-7378","authenticated-orcid":false,"given":"Qiaobing","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology School of Basic Medical Sciences, Southern Medical University  Guangzhou China"},{"name":"Department of Cardiology The Eighth Affiliated Hospital of Southern Medical University  Foshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"International Diabetes Federation. 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