biostudies-literatureKawaguchi MMinistry of Education, Science, Sports and Culture, JapanNCI NIH HHS1610-23https://www.ebi.ac.uk/biostudies/studies/S-EPMC5707200biostudies-literatureUnknown185(6)Hepatocyte growth factor activator inhibitor type 1 (HAI-1; official symbol SPINT1) is a membrane-associated serine proteinase inhibitor abundantly expressed in epithelial tissues. Genetically engineered mouse models demonstrated that HAI-1 is critical for epidermal function, possibly through direct and indirect regulation of cell surface proteases, such as matriptase and prostasin. To obtain a better understanding of the role of HAI-1 in maintaining epidermal integrity, we performed ultrastructural analysis of Spint1-deleted mouse epidermis and organotypic culture of an HAI-1 knockdown (KD) human keratinocyte cell line, HaCaT. We found that the aggregation of tonofilaments to desmosomes was significantly reduced in HAI-1-deficient mouse epidermis with decreased desmosome number. Similar fThe American journal of pathologyHepatocyte growth factor activator inhibitor type 1 maintains the assembly of keratin into desmosomes in keratinocytes by regulating protease-activated receptor 2-dependent p38 signaling.PMC570720025860166R01 CA12322324390099P30 CA051008Kanemaru AKawaguchi MYamamoto KBaba TSawaguchi AJohnson MDLin CYFukushima TKataoka HfalseHepatocyte growth factor activator inhibitor type 1 maintains the assembly of keratin into desmosomes in keratinocytes by regulating protease-activated receptor 2-dependent p38 signaling.Hepatocyte growth factor activator inhibitor type 1 (HAI-1; official symbol SPINT1) is a membrane-associated serine proteinase inhibitor abundantly expressed in epithelial tissues. Genetically engineered mouse models demonstrated that HAI-1 is critical for epidermal function, possibly through direct and indirect regulation of cell surface proteases, such as matriptase and prostasin. To obtain a better understanding of the role of HAI-1 in maintaining epidermal integrity, we performed ultrastructural analysis of Spint1-deleted mouse epidermis and organotypic culture of an HAI-1 knockdown (KD) human keratinocyte cell line, HaCaT. We found that the aggregation of tonofilaments to desmosomes was significantly reduced in HAI-1-deficient mouse epidermis with decreased desmosome number. Similar f2015-01-01T00:00:00Z2015 Jun2025-04-04T13:36:01.254Z2019-03-27T03:03:20ZS-EPMC57072002584236610.1016/j.ajpath.2015.02.009