Recent studies indicate that umbilical cord stem cells are cytoprotective against several disorders. One critical limitation in using stem cells is reduction in their viability under stressful conditions, such as diabetes. However, the molecular intricacies responsible for diabetic conditions are not fully elucidated. In this study, we found that high glucose (HG) conditions induced loss of chaperone homeostasis, stabilized PTEN, triggered the downstream signaling cascade, and induced apoptosis and oxidative stress in Wharton's jelly derived mesenchymal stem cells (WJMSCs). Increased Carboxyl terminus of Hsc70 interacting protein (CHIP) expression promoted phosphatase and tensin homolog (PTEN) degradation via the ubiquitin-proteasome system and shortened its half-life during HG stress. Docking studies confirmed the interaction of CHIP with PTEN and FOXO3a with the Bim promoter region. Further, it was found that the chaperone system is involved in CHIP-mediated PTEN proteasomal degradation. CHIP depletion stabilizes PTEN whereas PTEN inhibition showed an inverse effect. CHIP overactivation suppressed the binding of FOXO3a with bim. Coculturing CHIP overexpressed WJMSCs suppressed HG-induced apoptosis and oxidative stress in embryo derived cardiac cell lines. CHIP overexpressing and PTEN silenced WJMSCs ameliorated diabetic effects in streptozotocin (STZ) induced diabetic rats and further improved their body weight and heart weight, and rescued from hyperglycemia-induced cardiac injury. Considering these, the current study suggests that CHIP confers resistance to apoptosis and acts as a potentiation factor in WJMSCs to provide protection from degenerative effects of diabetes.

中文翻译：

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沃顿商学院果冻来源间充质干细胞中 Hsc70 相互作用蛋白 (CHIP) 羧基末端的 E3 连接酶活性提高了它们在高血糖应激下的持久性，并促进了对糖尿病心脏损伤的预防作用

最近的研究表明，脐带干细胞对多种疾病具有细胞保护作用。使用干细胞的一个关键限制是它们在压力条件下（例如糖尿病）的生存能力降低。然而，导致糖尿病状况的分子复杂性尚未完全阐明。在这项研究中，我们发现高葡萄糖 (HG) 条件会导致伴侣蛋白稳态的丧失，稳定 PTEN，触发下游信号级联，并诱导沃顿商学院果冻源间充质干细胞 (WJMSCs) 的细胞凋亡和氧化应激。Hsc70 相互作用蛋白 (CHIP) 表达的羧基末端增加通过泛素-蛋白酶体系统促进磷酸酶和张力蛋白同源物 (PTEN) 降解，并在 HG 应激期间缩短其半衰期。Bim启动子区域。此外，发现分子伴侣系统参与 CHIP 介导的 PTEN 蛋白酶体降解。CHIP 消耗使 PTEN 稳定，而 PTEN 抑制显示出相反的效果。CHIP过度激活抑制FOXO3a与bim的结合. 共培养 CHIP 过表达的 WJMSCs 抑制了胚胎来源的心脏细胞系中 HG 诱导的细胞凋亡和氧化应激。CHIP 过表达和 PTEN 沉默 WJMSCs 改善了链脲佐菌素 (STZ) 诱导的糖尿病大鼠的糖尿病效应，并进一步改善了它们的体重和心脏重量，并从高血糖引起的心脏损伤中解救出来。考虑到这些，目前的研究表明，CHIP 赋予对细胞凋亡的抵抗力，并在 WJMSCs 中充当增强因子，以防止糖尿病的退行性影响。