Mmp14-dependent remodeling of the pericellular-dermal collagen interface governs fibroblast survival

• Published in: The Journal of cell biology Vol. 223; no. 9; p. 1
• Main Authors: Sabeh, Farideh, Li, Xiao-Yan, Olson, Adam W, Botvinick, Elliot, Kurup, Abhishek, Gimenez, Luis E, Cho, Jung-Sun, Weiss, Stephen J
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 02.09.2024
• Subjects: Animals; Apoptosis; Cell activation; Cell death; Cell Survival; Cells, Cultured; Cellular stress response; Collagen; Collagen (type I); Collagen Type I - genetics; Collagen Type I - metabolism; Dermis - cytology; Dermis - metabolism; Extracellular matrix; Extracellular Matrix - metabolism; Fibrils; Fibroblasts; Fibroblasts - metabolism; In vivo methods and tests; Integrin beta1 - genetics; Integrin beta1 - metabolism; Matrix metalloproteinase; Matrix Metalloproteinase 14 - genetics; Matrix Metalloproteinase 14 - metabolism; Matrix metalloproteinases; Metalloproteinase; Mice; Mice, Inbred C57BL; Mice, Knockout; Proteolysis; Skin; Skin - metabolism; Survival; Survival factor; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b1
• ISSN: 0021-9525; 1540-8140; 1540-8140
• DOI: 10.1083/jcb.202312091

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.