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C-CBL is required for inhibition of angiogenesis through modulating JAK2/STAT3 activity in ROP development

Shimei Chen1, Qiao Sun1, Dandan Sun1

  • 1Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China; Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, 200080, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, 200080, China; National Clinical Research Center for Eye Diseases, Shanghai, 20080, China; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, 20080, China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|October 30, 2020
PubMed
Abstract

Insights

C-CBL inhibits retinal neovascularization in retinopathy of prematurity (ROP) by regulating the JAK2/STAT3/VEGF pathway. This suggests C-CBL is a potential therapeutic target for ROP treatment.

Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Developmental Biology

Background:

  • Retinopathy of prematurity (ROP) incidence is rising, with current treatments yielding suboptimal outcomes.
  • Understanding the molecular mechanisms of ROP is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the role of C-CBL in retinal angiogenesis during ROP.
  • To evaluate C-CBL as a potential therapeutic target for ROP.

Main Methods:

  • Utilized mouse retina microvascular endothelial cells (mRMECs) and a mouse model of oxygen-induced retinopathy (OIR).
  • Employed molecular, cellular, and histopathological approaches, including c-Cbl overexpression and siRNA knockdown.
  • Assessed retinal neovascularization and avascular status via immunofluorescence, whole-mounts, and H&E staining.

Main Results:

  • C-CBL negatively regulates the JAK2/STAT3/VEGF signaling axis in a ubiquitination-dependent manner, inhibiting neovascularization.
  • Knockdown of c-Cbl in mRMECs increased JAK2/STAT3/VEGF signaling and neovascularization, effects reversible by JAK2 inhibition.
  • In OIR mice, c-Cbl knockdown exacerbated retinal neovascularization, while c-Cbl overexpression reduced it.

Conclusions:

  • C-CBL plays a critical role in suppressing neovascularization during ROP development.
  • C-CBL acts by inhibiting JAK2/STAT3-dependent angiogenesis.
  • C-CBL represents a promising novel therapeutic target for treating retinopathy of prematurity.
Keywords:
AngiogenesisJAK2/STAT3/VEGF signaling pathwayRetinopathy of prematurityc-Cbl

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