The Expression of Circ-Astn1 Inhibits High Glucose Induced Endothelial Progenitor Cell Dysfunction by Activating

Shiying Huang1,2, Minjie Xu1,3, Maoquan Li1,3

  • 1Department of Interventional & Vascular Surgery, Tenth People's Hospital of Tongji University, Shanghai, China.

Endocrine Research
|June 13, 2024
PubMed
Abstract

Insights

Circular RNA circ-Astn1 protects against high glucose-induced endothelial cell damage in diabetes. It targets the miR-138-5p/SIRT5 pathway, promoting autophagy and suppressing apoptosis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Diabetes mellitus (DM) and its complications represent a significant global health challenge.
  • Circular RNAs (circRNAs) are emerging as key regulators of gene expression in various biological processes.
  • The specific roles of circRNAs in the pathogenesis of DM remain largely unexplored.

Purpose of the Study:

  • To investigate the expression and function of circRNAs in endothelial progenitor cells (EPCs) under high glucose (HG) conditions relevant to DM.
  • To elucidate the molecular mechanisms underlying the role of circ-Astn1 in HG-induced endothelial cell dysfunction.

Main Methods:

  • High-throughput sequencing of circRNAs in EPCs exposed to HG.
  • Bioinformatics analysis to identify potential targets and regulatory pathways.
  • Luciferase reporter assays, angiogenic differentiation assays, flow cytometry for apoptosis, and RT-qPCR to validate findings.

Main Results:

  • circ-Astn1 expression was downregulated in EPCs under HG conditions.
  • Overexpression of circ-Astn1 protected endothelial cells from HG-induced damage, including apoptosis and impaired vascular differentiation.
  • circ-Astn1 was found to target both miR-138-5p and SIRT5, with SIRT5 upregulation and autophagy promotion observed.

Conclusions:

  • circ-Astn1 plays a protective role against high glucose-induced endothelial cell damage in diabetes.
  • The protective mechanism involves targeting the miR-138-5p/SIRT5 axis, enhancing SIRT5 expression, and promoting autophagy.
  • circ-Astn1 represents a potential therapeutic target for managing diabetic vascular complications.

Related Concept Videos

Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.6K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.5K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.3K