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SH2B1 promotes apoptosis in diabetic cataract via p38 MAPK pathway

Xiaohui Jiang1, Liming Xu1, Boyue Xu2

  • 1Eye Hospital of Wenzhou Medical University at Hangzhou, 618 East Fengqi Road, Hangzhou 310000, Zhejiang, China.

Iscience
|February 3, 2025
PubMed

Insights

Diabetic cataract (DC) mechanisms were clarified by identifying SH2 domain-containing adapter protein B1 (SH2B1) as crucial. Reduced SH2B1 impacts lens cells, suggesting new therapeutic targets for diabetic eye disease.

Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Endocrinology

Background:

  • Diabetes mellitus significantly increases cataract risk.
  • The precise molecular mechanisms underlying diabetic cataract (DC) remain incompletely understood.
  • Lens anterior capsule protein expression differences between DC and age-related cataract are largely unexplored.

Purpose of the Study:

  • To elucidate the molecular mechanisms of diabetic cataract (DC) pathogenesis.
  • To identify key proteins involved in DC progression using quantitative proteomics.
  • To investigate the role of SH2 domain-containing adapter protein B1 (SH2B1) in DC.

Main Methods:

  • Quantitative proteomics to analyze protein expression in lens anterior capsules.
  • Polymerase chain reaction (PCR) and western blotting to validate protein expression.
  • In vitro studies using high-glucose (HG) cultured human lens epithelial cells and in vivo studies with diet-induced obese mice.

Main Results:

  • SH2 domain-containing adapter protein B1 (SH2B1) was identified as a critical protein in DC.
  • Reduced SH2B1 expression was observed in patient samples, obese mice, and HG-cultured cells.
  • High glucose conditions induced decreased cell proliferation, increased migration and apoptosis, modulated Bcl2 and caspase-3 expression, and affected the p38 MAPK pathway.
  • SH2B1 overexpression ameliorated HG-induced cellular changes and influenced the p38 MAPK pathway.

Conclusions:

  • SH2B1 plays a significant role in the pathogenesis of diabetic cataract.
  • The p38 MAPK signaling pathway is implicated in DC development.
  • SH2B1 and the p38 MAPK pathway represent potential therapeutic targets for halting or slowing diabetic cataract progression.
Keywords:
Cellular physiologyMolecular biology

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