Scholarlink

<p>This study elucidated the mechanistic role of the Suppressor of Cytokine Signaling 5 (SOCS5) in diabetic retinopathy (DR), focusing on DNA damage and cellular senescence pathways. Utilizing both in vitro (high glucose (HG)-induced human retinal microvascular endothelial cells (HRMECs)) and in vivo (streptozotocin-induced DR mouse models) approaches, we demonstrated that SOCS5 was significantly upregulated in DR. SOCS5 knockdown mitigated retinal tissue damage, vascular leakage, and apoptosis in DR mice while reducing DNA damage and cellular senescence in HG-stimulated HRMECs. Mechanistically, SOCS5 promoted DR progression by regulating the expression of Cyclin-Dependent Kinase Inhibitor 1 A (CDKN1A), a key mediator of cell cycle arrest and senescence. Furthermore, we identified POU Class 2 Homeobox 1 (POU2F1) as an upstream transcriptional activator of SOCS5, forming a novel POU2F1-SOCS5-CDKN1A axis that drove DR pathogenesis. Inhibition of POU2F1 and SOCS5 ameliorated DR-related pathology in mice, suggesting a novel therapeutic strategy. These findings reveal a previously unrecognized signaling pathway in DR and highlight SOCS5 as a promising target for intervention.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Mechanistic insights into SOCS5-related DNA damage and cellular senescence in diabetic retinopathy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月1日

查看全文
  • Di Yang,
  • Siduo Lu,
  • Hongmei Liu,
  • You Zhou,
  • Hua Zhong

摘要

This study elucidated the mechanistic role of the Suppressor of Cytokine Signaling 5 (SOCS5) in diabetic retinopathy (DR), focusing on DNA damage and cellular senescence pathways. Utilizing both in vitro (high glucose (HG)-induced human retinal microvascular endothelial cells (HRMECs)) and in vivo (streptozotocin-induced DR mouse models) approaches, we demonstrated that SOCS5 was significantly upregulated in DR. SOCS5 knockdown mitigated retinal tissue damage, vascular leakage, and apoptosis in DR mice while reducing DNA damage and cellular senescence in HG-stimulated HRMECs. Mechanistically, SOCS5 promoted DR progression by regulating the expression of Cyclin-Dependent Kinase Inhibitor 1 A (CDKN1A), a key mediator of cell cycle arrest and senescence. Furthermore, we identified POU Class 2 Homeobox 1 (POU2F1) as an upstream transcriptional activator of SOCS5, forming a novel POU2F1-SOCS5-CDKN1A axis that drove DR pathogenesis. Inhibition of POU2F1 and SOCS5 ameliorated DR-related pathology in mice, suggesting a novel therapeutic strategy. These findings reveal a previously unrecognized signaling pathway in DR and highlight SOCS5 as a promising target for intervention.