The RING E3 ligase RLIM drives oxidative stress-induced stem cell dysfunction through MDM2-p53 signaling.
Xiaoyue Li, Caiqi Shen, Yajie Li, Lijun Wu et al.
Kernaussage
The RLIM-MDM2-p53 signaling axis drives oxidative stress-induced stem cell dysfunction by promoting MDM2 ubiquitination and degradation, leading to p53 stabilization, autophagy suppression, and accelerated senescence, ultimately impairing wound healing.
Abstract
Chronic diabetic ulcers present a persistent challenge due to delayed wound healing. At the wound site, oxidative stress impairs stem cell survival and differentiation, accelerates senescence, and impairs autophagy. RLIM was identified as a critical regulator in human umbilical cord mesenchymal stem cells (hUCMSCs), where oxidative stress-induced RLIM upregulation leads to MDM2 degradation and stabilization of p53. Functionally, RLIM upregulation under oxidative stress inhibited autophagy, induced cellular senescence, and significantly impaired angiogenesis, cell migration, and immunomodulatory functions, ultimately hindering diabetic wound healing in vivo. These results highlight the RLIM-MDM2-p53 signaling axis as a pivotal pathway governing stem cell senescence and function under oxidative stress, offering promising therapeutic targets to enhance stem cell-based approaches for diabetic wound repair.
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Quelle: PubMed Central / National Library of Medicine (NLM). Apollion steht in keiner Verbindung mit NLM und wird von NLM nicht empfohlen. Evidenzgrade bewerten die methodische Studienqualität — nicht die inhaltliche Richtigkeit.
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