Article ; Online: HAI-1 is required for the novel role of FGFBP1 in maintenance of cell morphology and F-actin rearrangement in human keratinocytes.
2023 Volume 36, Issue 4, Page(s) 1403–1415
Abstract: Formation and maintenance of skin barrier function require tightly controlled membrane-associated proteolysis, in which the integral membrane Kunitz-type serine protease inhibitor, HAI-1, functions as the primary inhibitor of the membrane-associated ... ...
| Abstract | Formation and maintenance of skin barrier function require tightly controlled membrane-associated proteolysis, in which the integral membrane Kunitz-type serine protease inhibitor, HAI-1, functions as the primary inhibitor of the membrane-associated serine proteases, matriptase and prostasin. Previously, HAI-1 loss in HaCaT human keratinocytes resulted in an expected increase in prostasin proteolysis but a paradoxical decrease in matriptase proteolysis. The paradoxical decrease in shed active matriptase is further investigated in this study with an unexpected discovery of novel functions of fibroblast growth factor-binding protein 1 (FGFBP1), which acts as an extracellular ligand that can rapidly elicit F-actin rearrangement and subsequently affect the morphology of human keratinocytes. This novel growth factor-like function is in stark contrast to the canonical activity of this protein through interactions with FGFs for its pathophysiological functions. This discovery began with the observation that HAI-1 KO HaCaT cells lose the characteristic cobblestone morphology of the parental cells and exhibit aberrant F-actin formation along with altered subcellular targeting of matriptase and HAI-2. The alterations in cell morphology and F-actin status caused by targeted HAI-1 deletion can be restored by treatment with conditioned medium from parental HaCaT cells, in which FGFBP1 was identified by tandem mass spectrometry. Recombinant FGFBP1 down to 1 ng/ml was able to revert the changes caused by HAI-1 loss. Our study reveals a novel function of FGFBP1 in the maintenance of keratinocyte morphology, which depends on HAI-1. |
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| MeSH term(s) | Humans ; Actins/metabolism ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism ; Keratinocytes/metabolism ; Proteolysis ; Proteinase Inhibitory Proteins, Secretory/metabolism ; Intercellular Signaling Peptides and Proteins/metabolism | |||||
| Chemical Substances | Actins ; Membrane Glycoproteins ; Proteinase Inhibitory Proteins, Secretory ; FGFBP1 protein, human (139946-12-6) ; Intercellular Signaling Peptides and Proteins | |||||
| Language | English | |||||
| Publishing date | 2023-04-19 | |||||
| Publishing country | Japan | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 1149134-6 | |||||
| ISSN | 1749-0774 ; 0914-7470 | |||||
| ISSN (online) | 1749-0774 | |||||
| ISSN | 0914-7470 | |||||
| DOI | 10.1007/s13577-023-00906-6 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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