CHIP-overexpressing Wharton's jelly-derived mesenchymal stem cells attenuate hyperglycemia-induced oxidative stress-mediated kidney injuries in diabetic rats

Ayaz Ali, Marthandam Asokan Shibu, Chia Hua Kuo, Jeng Feng Lo, Ray Jade Chen, Cecilia Hsuan Day, Tsung Jung Ho, Vijaya PadmaViswanadha, Wei Wen Kuo, Chih Yang Huang

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Accumulating studies have demonstrated the protective roles of mesenchymal stem cells against several disorders. However, one of their crucial limitations is reduced viability under stress conditions, including the hyperglycemia induced by diabetes. The molecular mechanisms involved in diabetes-induced kidney injuries are not fully elucidated. In this study, we found that high glucose (HG) reduced human proximal tubular epithelial cell viability. Further, hyperglycemia induced oxidative stress-mediated apoptosis and fibrosis in HK-2 cells via activation of the mitogen-activated protein kinases (MAPKs) including c-Jun N-terminal kinase JNK and p38 kinase. Carboxyl terminus of HSP70 interacting protein (CHIP) overactivation considerably rescued cell viability under HG stress. Moreover, Western blot analysis, flow cytometry, and MitoSOX staining revealed that hyperglycemia-induced mitochondrial oxidative stress production and apoptosis were attenuated in CHIP-overexpressing Wharton's jelly-derived mesenchymal stem cells (WJMSCs). Co-culture with CHIP-expressing WJMSCs maintained HK-2 cell viability, and inhibited apoptosis and fibrosis by attenuating HG-induced ROS-mediated MAPK activation. CHIP-overexpressing WJMSCs also rescued the decreased kidney weight and hyperglycemia-induced kidney damage observed in streptozotocin-induced diabetic rats. Cumulatively, the current research findings demonstrate that CHIP suppresses hyperglycemia-induced oxidative stress and confers resistance to MAPK-induced apoptosis and fibrosis, and suggests that CHIP protects WJMSCs and the high quality WJMSCs have therapeutic effects against diabetes-induced kidney injuries.

Original languageEnglish
Pages (from-to)70-80
Number of pages11
JournalFree Radical Biology and Medicine
Volume173
DOIs
Publication statusPublished - Sep 2021

Keywords

  • Apoptosis
  • Carboxyl terminus of HSP70 interacting protein
  • Diabetes
  • Fibrosis
  • Rats
  • Wharton's jelly derived mesenchymal stem cells

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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