Related Experiment Video

Updated: Mar 16, 2026

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
10:43

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration

Published on: May 19, 2016

7.1K

miRNA-1283 Regulates the PERK/ATF4 Pathway in Vascular Injury by Targeting ATF4

Ling He1, Jing Yuan1, Qingyun Xu1

  • 1Department of Chinese Medicine, Medical College of Jinan University, Guangzhou, 510632, Guangdong Province, PR China.

Plos One
|August 19, 2016
PubMed
Abstract

Insights

MicroRNA-1283 (miR-1283) inhibits activating transcription factor 4 (ATF4), regulating the PERK-eIF2α-ATF4 pathway. This mechanism is critical for endothelial cell injury in hypertension.

Area of Science:

  • Molecular Biology
  • Cardiovascular Research
  • Cell Biology

Background:

  • Previous studies identified differential mRNA and microRNA (miRNA) levels in hypertensive patients, linked to endoplasmic reticulum stress (ERS) and activating transcription factor 4 (ATF4).
  • Gene prediction suggested synergistic effects between ATF4 and miR-1283, highlighting ATF4's role in ERS pathways, particularly the PERK pathway.
  • The PERK pathway involves eukaryotic translation initiation factor 2α (eIF2α) phosphorylation and ATF4 activation.

Purpose of the Study:

  • To investigate the regulatory effects of miR-1283 and ATF4 on the PERK-eIF2α-ATF4 signaling pathway.
  • To elucidate the role of this pathway in human umbilical vein endothelial cells (HUVECs) and mouse models.

Main Methods:

  • Luciferase activity assays were employed to verify the relationship between miR-1283 and ATF4.
  • In vivo and in vitro experiments were conducted to observe the regulatory effects of miR-1283 and ATF4 on the PERK-eIF2α-ATF4 signaling pathway.

Main Results:

  • The study confirmed that ATF4 is a direct target gene of miR-1283.
  • miR-1283 was shown to regulate the PERK-eIF2α-ATF4 signaling pathway by inhibiting ATF4 expression.

Conclusions:

  • miR-1283 plays a critical role in inducing injury in HUVECs and mouse heart tissue by regulating the PERK-eIF2α-ATF4 pathway via ATF4 inhibition.
  • These findings provide insights into the molecular mechanisms underlying endothelial cell damage in hypertension.

More Related Videos

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

1.0K
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis11:44

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis

Published on: March 30, 2019

8.1K

Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.0K
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...
3.9K
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...
6.1K
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.7K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.2K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
10.2K