2015
DOI: 10.1016/j.ajpath.2015.02.009
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Hepatocyte Growth Factor Activator Inhibitor Type 1 Maintains the Assembly of Keratin into Desmosomes in Keratinocytes by Regulating Protease-Activated Receptor 2–Dependent p38 Signaling

Abstract: Hepatocyte growth factor activator inhibitor type 1 (HAI-1; official symbol SPINT1) is a membraneassociated 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… Show more

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Cited by 22 publications
(25 citation statements)
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“…However, the Spint1 −/− neonates died within 16 days of birth, showing abnormal epidermal keratinization, cuticle defect in hair and whiskers, decreased barrier function of the skin and dermal inflammation (Fig. b) . The disturbance of epidermal integrity by Hai‐1/Spint1 deficiency was also reported in a zebrafish mutant model .…”
Section: Hai‐1/spint1 and Hai‐2/spint2: Emerging Guardians Of Epithelmentioning
confidence: 61%
“…However, the Spint1 −/− neonates died within 16 days of birth, showing abnormal epidermal keratinization, cuticle defect in hair and whiskers, decreased barrier function of the skin and dermal inflammation (Fig. b) . The disturbance of epidermal integrity by Hai‐1/Spint1 deficiency was also reported in a zebrafish mutant model .…”
Section: Hai‐1/spint1 and Hai‐2/spint2: Emerging Guardians Of Epithelmentioning
confidence: 61%
“…The activity was expressed either by relative fluorescence unit (RFU) at each time point or the calculated maximum slope of the hydrolysis rate (velocity max: V max ). For transient silencing of matriptase, two kinds of small interfering RNA (siRNA) were used as described previously . One (mat siRNA #1) was Stealth™ siRNA (Invitrogen) and the sequence was 5′‐GCGUGUACACAAGGCUCCCUCUGUU‐3′.…”
Section: Methodsmentioning
confidence: 99%
“…Therefore, we hypothesized that the loss of HAI‐1 might have a causal role in the recruitment of CAFs. Some evidence suggests that insufficient HAI‐1 activity enhances pericellular serine protease activities, particularly of matriptase . Matriptase is one of the most studied TTSPs and has important roles in carcinogenesis and cancer progression .…”
mentioning
confidence: 99%
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“…Further studies suggest that the type II keratin KRT5 is a major determinant of desmosome stability (Loschke et al 2016). In addition to PKCa, p38 MAP kinase (MAPK) signaling downstream from the serine protease inhibitor SPINT1 participates in the interaction of keratins and desmosomal proteins (Kawaguchi et al 2015).…”
Section: Interdependence Of Keratins and Desmosomesmentioning
confidence: 99%