Roles of HAI-1, a membrane-anchored serine protease inhibitor, in maintaining keratinocyte morphology

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860166
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: University of Miyazaki
• Principal Investigator: KAWAGUCHI Makiko 宮崎大学, 医学部, 助教 (90405598)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 表皮 / セリンプロテアーゼ / セリンプロテアーゼインヒビター / p38MAPK / PAR-2

Outline of Final Research Achievements

To obtain a better understanding of the role of HAI-1 in maintaining epidermal integrity, we performed ultrastructural analysis of Hai-1-deficient 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 with decreased desmosome number. Similar findings were observed in HAI-1 KD HaCaT organotypic cultures. Immunohistochemical analyses demonstrated that p38 was activated in Hai-1-deficient keratinocytes. Silencing of protease-activated receptor-2 (PAR-2) abrogated the activation of p38 in HAI-1 KD HaCaT cells. Furthermore, treatment of HAI-1 KD HaCaT cells by p38 inhibitor abrogated the morphological abnormalities in the organotypic culture. These results suggest that HAI-1 have a critical role in maintaining normal keratinocyte morphology through regulation of PAR-2-dependent p38 MAP kinase signaling.

Free Research Field

実験病理学、分子生物学