MSC-derived exosomal lncRNA SNHG7 suppresses endothelial-mesenchymal transition and tube formation in diabetic retinopathy via miR-34a-5p/XBP1 axis.

Abstract

AIMS:

Diabetic retinopathy (DR) is the most common complication of type 2 diabetes mellitus, which could result in visual impairment. Accumulating studies have shown the implication of long non-coding RNAs (lncRNAs) in the pathogenesis of DR. Our aims are to investigate whether lncRNA SNHG7 plays a role during DR pathogenesis.

MAIN METHODS:

Human retinal microvascular endothelial cells (HRMECs) were treated with high glucose (HG) to build cell model. Relative expression of RNAs were examined using qPCR, and western blot or immunofluorescence analysis was adopted to detect the protein expression. Cell viability, migration and angiogenic capacity of HRMECs were estimated through CCK-8, transwell and tube formation experiments, respectively. Dual-luciferase reporter and RNA pull down assays were employed to verify the interplay between miR-34a-5p and SNHG7 or XBP1. Mesenchymal stem cells (MSCs) were identified by examining typical surface makers using flow cytometry and the differentiation abilities via Alizarin red, Oil red O and Alcian blue staining. MSC-derived exosomes were verified by transmission electron microscopy and western blot.

KEY FINDINGS:

LncRNA SNHG7 sponged to and negatively regulated miR-34a-5p. SNHG7 overexpression repressed HG induced endothelial-mesenchymal transition (EndMT) and tube formation of HRMECs, while miR-34a-5p overexpression could reverse this effect. miR-34a-5p targeted and negative regulated XBP1. Knockdown of miR-34a-5p repressed HG induced EndMT and tube formation, which were partially blocked by XBP1 inhibition. MSC-derived exosomes could transfer SNHG7 to HRMECs and modulated EndMT and tube formation.

SIGNIFICANCE:

The MSC-derived exosomal lncRNA SNHG7 suppresses EndMT and tube formation in HRMECs via miR-34a-5p/XBP1 axis.

• Authors: Xin Cao, Li-Dan Xue, Yue Di, Tao Li, Ya-Jing Tian, Yu Song
• Journal: Life sciences (Life Sci) Vol. 272 Pg. 119232 (May 01 2021) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 33600866 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• MIRN34 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• X-Box Binding Protein 1
• XBP1 protein, human
• Glucose

Topics

• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Cell Survival (genetics)
• Diabetes Complications (genetics, metabolism)
• Diabetes Mellitus, Type 2 (metabolism)
• Diabetic Retinopathy (genetics)
• Endothelial Cells (metabolism)
• Exosomes (metabolism)
• Glucose (metabolism)
• Humans
• Mesenchymal Stem Cells
• MicroRNAs (genetics)
• RNA, Long Noncoding (genetics)
• Retina (metabolism)
• Signal Transduction (genetics)
• X-Box Binding Protein 1 (metabolism)