BMP1 is not required for lung fibrosis in mice.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
31 03 2022
31 03 2022
Historique:
received:
11
11
2021
accepted:
24
03
2022
entrez:
1
4
2022
pubmed:
2
4
2022
medline:
5
4
2022
Statut:
epublish
Résumé
Bone morphogenetic protein 1 (BMP1) belongs to the astacin/BMP1/tolloid-like family of zinc metalloproteinases, which play a fundamental role in the development and formation of extracellular matrix (ECM). BMP1 mediates the cleavage of carboxyl terminal (C-term) propeptides from procollagens, a crucial step in fibrillar collagen fiber formation. Blocking BMP1 by small molecule or antibody inhibitors has been linked to anti-fibrotic activity in the preclinical models of skin, kidney and liver fibrosis. Therefore, we reason that BMP1 may be important for the pathogenesis of lung fibrosis and BMP1 could be a potential therapeutic target for progressive fibrotic disease such as idiopathic pulmonary fibrosis (IPF). Here, we observed the increased expression of BMP1 in both human IPF lungs and mouse fibrotic lungs induced by bleomycin. Furthermore, we developed an inducible Bmp1 conditional knockout (cKO) mouse strain. We found that Bmp1 deletion does not protect mice from lung fibrosis triggered by bleomycin. Moreover, we found no significant impact of BMP1 deficiency upon C-term propeptide of type I procollagen (CICP) production in the fibrotic mouse lungs. Based on these results, we propose that BMP1 is not required for lung fibrosis in mice and BMP1 may not be considered a candidate therapeutic target for IPF.
Identifiants
pubmed: 35361882
doi: 10.1038/s41598-022-09557-3
pii: 10.1038/s41598-022-09557-3
pmc: PMC8971496
doi:
Substances chimiques
Procollagen
0
Bleomycin
11056-06-7
Bmp1 protein, mouse
EC 3.4.24.19
Bone Morphogenetic Protein 1
EC 3.4.24.19
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5466Informations de copyright
© 2022. The Author(s).
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