Mmp14-dependent remodeling of the pericellular-dermal collagen interface governs fibroblast survival.
Animals
Matrix Metalloproteinase 14
/ metabolism
Fibroblasts
/ metabolism
Cell Survival
Apoptosis
Mice
Mice, Knockout
Collagen Type I
/ metabolism
Integrin beta1
/ metabolism
Transforming Growth Factor beta1
/ metabolism
Dermis
/ metabolism
Cells, Cultured
Extracellular Matrix
/ metabolism
Mice, Inbred C57BL
Skin
/ metabolism
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
02 Sep 2024
02 Sep 2024
Historique:
received:
18
12
2023
revised:
10
05
2024
accepted:
30
05
2024
medline:
11
7
2024
pubmed:
11
7
2024
entrez:
11
7
2024
Statut:
ppublish
Résumé
Dermal fibroblasts deposit type I collagen, the dominant extracellular matrix molecule found in skin, during early postnatal development. Coincident with this biosynthetic program, fibroblasts proteolytically remodel pericellular collagen fibrils by mobilizing the membrane-anchored matrix metalloproteinase, Mmp14. Unexpectedly, dermal fibroblasts in Mmp14-/- mice commit to a large-scale apoptotic program that leaves skin tissues replete with dying cells. A requirement for Mmp14 in dermal fibroblast survival is recapitulated in vitro when cells are embedded within, but not cultured atop, three-dimensional hydrogels of crosslinked type I collagen. In the absence of Mmp14-dependent pericellular proteolysis, dermal fibroblasts fail to trigger β1 integrin activation and instead actuate a TGF-β1/phospho-JNK stress response that leads to apoptotic cell death in vitro as well as in vivo. Taken together, these studies identify Mmp14 as a requisite cell survival factor that maintains dermal fibroblast viability in postnatal dermal tissues.
Identifiants
pubmed: 38990714
pii: 276851
doi: 10.1083/jcb.202312091
pii:
doi:
Substances chimiques
Matrix Metalloproteinase 14
EC 3.4.24.80
Mmp14 protein, mouse
0
Collagen Type I
0
Integrin beta1
0
Transforming Growth Factor beta1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIH HHS
ID : R01-CA-071699-16-A1
Pays : United States
Organisme : Breast Cancer Research Foundation
Organisme : Margolies Family Discovery Fund for Cancer Research
Informations de copyright
© 2024 Sabeh et al.