2021
DOI: 10.1111/wrr.12938
|View full text |Cite
|
Sign up to set email alerts
|

Integrin α4β1 is required for IL‐1α‐ and Nrf2‐dependent, Cox‐2 induction in fibroblasts, supporting a mechanism that suppresses α‐SMA expression

Abstract: Growth and repair processes, both normal and pathological, require reciprocal interactions between cells and their microenvironment. Integrins are bidirectional, cell surface receptors that transduce mechanical and chemical signals to and from the extracellular matrix. We recently reported that keratinocyte α3β1 is required for interleukin (IL)-1α secretion. Importantly, IL-1α regulates fibroblast Cox-2 expression and prostaglandin E2 (PGE 2 ) secretion, thereby linking keratinocyte integrin function to a para… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

0
10
0

Year Published

2021
2021
2024
2024

Publication Types

Select...
6
1

Relationship

0
7

Authors

Journals

citations
Cited by 10 publications
(10 citation statements)
references
References 14 publications
0
10
0
Order By: Relevance
“…Either directly or through binding of GAGs and proteoglycans, FN also acts as a template for other ECM proteins such as fibrillins, collagens, elastin, or sequesters TGF-β1 through binding of LTBPs. 59,60 FN is recognized by integrins αvβ3, αvβ5, and α5β1 (all FNs), and α4β7, α4β1, and α9β1 (ED-A FN), 61 often in close proximity to FN-bound growth factors. 62 Some of these binding sites and FN self-assembly sites are 'cryptic', that is, only available either by insertion of the ED-A and ED-B splice domains or upon mechanical strain.…”
Section: Fibronectinmentioning
confidence: 99%
“…Either directly or through binding of GAGs and proteoglycans, FN also acts as a template for other ECM proteins such as fibrillins, collagens, elastin, or sequesters TGF-β1 through binding of LTBPs. 59,60 FN is recognized by integrins αvβ3, αvβ5, and α5β1 (all FNs), and α4β7, α4β1, and α9β1 (ED-A FN), 61 often in close proximity to FN-bound growth factors. 62 Some of these binding sites and FN self-assembly sites are 'cryptic', that is, only available either by insertion of the ED-A and ED-B splice domains or upon mechanical strain.…”
Section: Fibronectinmentioning
confidence: 99%
“…40,41 One possible theory is that the GM18 progressively released by the PLLA scaffold in vivo occupies the α 4 β 1 binding site, thus preventing EDA-FN-α 4 β 1 binding, and mitigating the profibrotic effect of this interaction. In fact, integrin α 4 β 1 controls fibroblast proliferation and TFGβ1 processing, 42 supporting a mechanism that suppresses α-SMA expression, a key molecular event in fibrosis dependent on microenvironmental cues, 15 regulating the phenotype in dermal fibroblasts. 40 Our in vitro results support this hypothesis, indeed in vitro treatment of fibroblasts with GM18 leads to a loss of the adhesion properties of these cells, thus indicating a functional GM18 occupancy of the α 4 β 1 binding site.…”
Section: ■ Discussionmentioning
confidence: 95%
“…13 The integrin α 4 β 1 plays a role in skin pathophysiology, where it forms part of the skin immune response, promotes the migration of neutrophils, 14 and regulates the differentiated state of fibroblasts based on microenvironmental cues. 15 It is also expressed in endothelial progenitor cells 16 and the vascular endothelium where it binds to VCAM-1, mediating leukocyte trafficking to sites of inflammation. 17 Based on these characteristics of α 4 β 1 , we decided to further explore the possible use of GM18 in skin wound healing.…”
Section: ■ Introductionmentioning
confidence: 99%
“…Keratinocytes have suggested roles in the regulation of the myofibroblast phenotype and profibrotic ECM during wound healing [233][234][235]. More recently, the keratinocyte secretion of IL-1α was demonstrated to restrain the myofibroblast phenotype, dependent on fibroblast integrin α4β1 expression and Cox-2/Nrf2 signalling [236,237].…”
Section: Immunomodulating Biomolecules For Fibrosis Attenuationmentioning
confidence: 99%