ADAM15 in Fibroblasts: Improving the Matrix Remodeling by Blocking the Action of Transforming Growth Factor-ß1.
Ann Clin Lab Sci
; 54(3): 363-370, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-39048163
ABSTRACT
OBJECTIVE:
During the progression of chronic idiopathic pulmonary fibrosis (IPF), maladaptive tissue remodeling including excessive extracellular matrix (ECM) deposition occurs, which eventually leads to architectural distortion and loss of organ function in organ fibrosis. ADAM15, which is highly expressed in the developing lungs and kidneys, is a transmembrane-anchored multidomain protein belonging to the family of metalloproteinases. Compared to the extensive studies about functions of matrix metalloproteinases (MMPs), less are discussed about ADAM15, particularly in function and mechanism involving fibrogenesis. Our study aims to fill in this gap.METHODS:
We identified ADAM15 as a novel antifibrotic mediator in lung fibrosis. We found that ADAM15 has cross-talks with transforming growth factor-ß1 (TGF-ß1), which is the most potent profibrotic mediator. We provided molecular and translational evidence that knockdown of ADAM15 accelerated fibrogenic response induced by TGF-ß1 and upregulation of ADAM15 rescued TGF-ß1-induced myofibroblast activation in part.RESULTS:
Overexpression of ADAM15 ameliorates fibrotic changes and ADAM15 deficiency exacerbates changes from fibroblast to myofibroblast in NIH/3T3. Results were also presented and identified by the intuitive immunofluorescence staining.CONCLUSION:
In this study, we uncover a new molecular mechanism of tissue fibrogenesis and identify ADAM15 as a potential therapeutic target in the treatment of fibrotic diseases.Key words
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
ADAM Proteins
/
Extracellular Matrix
/
Transforming Growth Factor beta1
/
Fibroblasts
/
Membrane Proteins
Limits:
Animals
/
Humans
Language:
En
Journal:
Ann Clin Lab Sci
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Estados Unidos