A major role of TWEAK/Fn14 axis as a therapeutic target for post-angioplasty restenosis

EBioMedicine
Nerea Méndez-BarberoLuis Miguel Blanco-Colio

Abstract

Tumor necrosis factor-like weak inducer of apoptosis (Tnfsf12; TWEAK) and its receptor Fibroblast growth factor-inducible 14 (Tnfrsf12a; Fn14) participate in the inflammatory response associated with vascular remodeling. However, the functional effect of TWEAK on vascular smooth muscle cells (VSMCs) is not completely elucidated. Next generation sequencing-based methods were performed to identify genes and pathways regulated by TWEAK in VSMCs. Flow-citometry, wound-healing scratch experiments and transwell migration assays were used to analyze VSMCs proliferation and migration. Mouse wire injury model was done to evaluate the role of TWEAK/Fn14 during neointimal hyperplasia. TWEAK up-regulated 1611 and down-regulated 1091 genes in VSMCs. Using a gene-set enrichment method, we found a functional module involved in cell proliferation defined as the minimal network connecting top TWEAK up-regulated genes. In vitro experiments in wild-type or Tnfrsf12a deficient VSMCs demonstrated that TWEAK increased cell proliferation, VSMCs motility and migration. Mechanistically, TWEAK increased cyclins (cyclinD1), cyclin-dependent kinases (CDK4, CDK6) and decreased cyclin-dependent kinase inhibitors (p15lNK4B) mRNA and protein expression. Downr...Continue Reading

Citations

Oct 2, 2020·Journal of Cellular Physiology·Yitian ZhangYumin Xia
Nov 16, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Guanting LiHongliang Huang
Jan 30, 2021·The Journal of Pathology·Jonay PovedaGema Ruiz-Hurtado
Sep 21, 2021·Reviews in Endocrine & Metabolic Disorders·Wiktoria RatajczakCatriona Kelly

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE114116

Methods Mentioned

BETA
RNA-seq
dissection
PCR
RNASeq
flow cytometry

Software Mentioned

NetworkMiner
R
RNASeq
DeSeq2
FatiGO
Babelomics suite
Pro Plus
Bioconductor
ImageJ
TWEAK

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis