Chondroitin sulfate enhances the barrier function of basement membrane assembled by heparan sulfate

Chenqi Tao, Neoklis Makrides, Jen Zen Chuang, Yihua Wu, Steven E. Brooks, Jeffrey D. Esko, Ching Hwa Sung, Xin Zhang

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Glycosaminoglycans are ubiquitously expressed polysaccharides that are attached to proteoglycans. Here, we showed that ablation of the heparan sulfate (HS) polymerase Ext1 in retinal progenitor cells did not affect initial progression of retinal angiogenesis, but it disrupted the pruning of blood vessels and establishment of arterioles and venules. In the absence of retinal HS, blood vessels were also vulnerable to high oxygen tension in early postnatal stages, which could be rescued by exogenous vascular endothelial growth factor (VEGF), consistent with the role of retinal HS in the fine-tuning of VEGF signaling. Furthermore, we observed that the retinal inner limiting membrane (ILM) was disrupted by deletion of Ext1 in a timing-specific manner, suggesting that retinal HS is required for the assembly but not the maintenance of the basement membrane. Lastly, we showed that further deletion of C4st1, a chondroitin sulfate (CS) sulfation enzyme, did not affect the assembly of the ILM but, when combined with Ext1 deletion, it aggravated the retinal permeability by disrupting the retinal glycocalyx. These results demonstrate an important role of CS and HS in establishing the barrier function of the extracellular matrix.

Original languageEnglish (US)
Article numberdev200569
JournalDevelopment (Cambridge)
Volume149
Issue number12
DOIs
StatePublished - Jun 2022
Externally publishedYes

Keywords

  • Angiogenesis
  • Astrocyte
  • Basement membrane
  • Chondroitin sulfate
  • Glycocalyx
  • Retina

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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