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SIPA1 promotes angiogenesis by regulating VEGF secretion in Müller cells through STAT3 activation

Yanhong Fang1,2, Qionghua Wang2, Lanyue Zhang2

  • 1Department of Ophthalmology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Heliyon
|February 5, 2024
PubMed

Insights

Signal-induced proliferation-associated protein 1 (SIPA1) promotes diabetic retinopathy (DR) by increasing vascular endothelial growth factor (VEGF) secretion in Müller cells via the STAT3 pathway. This highlights SIPA1 as a potential therapeutic target for DR.

Area of Science:

  • Ophthalmology
  • Diabetology
  • Cell Biology

Background:

  • Diabetic retinopathy (DR) is a leading cause of vision loss due to diabetes-induced retinal microvasculature damage.
  • Müller cells are critical in regulating the retinal vascular microenvironment.
  • Chronic hyperglycemia in diabetes exacerbates retinal damage.

Purpose of the Study:

  • To investigate the role of signal-induced proliferation-associated protein 1 (SIPA1) in Müller cell-mediated angiogenesis.
  • To elucidate the molecular mechanisms by which SIPA1 influences retinal vascularization in the context of diabetes.

Main Methods:

  • Proteomics and database analysis to identify SIPA1 expression changes.
  • Endothelial cell function assays to assess vascular effects.
  • Western blot and STAT3 inhibition (STATTIC) to study signaling pathways.

Main Results:

  • SIPA1 expression is upregulated in Müller cells under high glucose conditions.
  • SIPA1 promotes vascular endothelial growth factor (VEGF) secretion and retinal vascular endothelial cell migration.
  • SIPA1 activates STAT3 phosphorylation and nuclear translocation, mediating VEGF expression.

Conclusions:

  • SIPA1 promotes pro-angiogenic factor secretion in Müller cells by activating the STAT3 signaling pathway.
  • SIPA1 plays a significant role in the pathogenesis of diabetic retinopathy.
  • SIPA1 represents a potential therapeutic target for managing diabetic retinopathy.
Keywords:
AngiogenesisMüller cellsSIPA1STAT3VEGF

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