Loss of hepatocyte growth factor activator inhibitor type 1 (HAI-1) upregulates MMP-9 expression and induces degradation of the epidermal basement membrane.

Autor: Weiting L; Section of Oncopathology and Morphological Pathology, Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miazaki, 889-1692, Japan., Kawaguchi M; Section of Oncopathology and Morphological Pathology, Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miazaki, 889-1692, Japan. kawaguchi@med.miyazaki-u.ac.jp., Fukushima T; Section of Oncopathology and Morphological Pathology, Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miazaki, 889-1692, Japan., Sato Y; Section of Oncopathology and Morphological Pathology, Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miazaki, 889-1692, Japan.
Jazyk: angličtina
Zdroj: Human cell [Hum Cell] 2024 Dec 28; Vol. 38 (1), pp. 36. Date of Electronic Publication: 2024 Dec 28.
DOI: 10.1007/s13577-024-01159-7
Abstrakt: Hepatocyte growth factor activator inhibitor type 1 (HAI-1), which is encoded by the SPINT1 gene, is a membrane-associated serine proteinase inhibitor abundantly expressed in epithelial tissues. We had previously demonstrated that HAI-1 is critical for placental development, epidermal keratinization, and maintenance of keratinocyte morphology by regulating cognate proteases, matriptase and prostasin. After performing ultrastructural analysis of Spint1-deleted skin tissues, our results showed that Spint1-deleted epidermis exhibited partially disrupted epidermal basement-membrane structures. Matrix metalloproteinases-9 (MMP-9) expression levels were upregulated in Spint1-deleted primary cultured keratinocytes and SPINT1 knockout (KO) HaCaT cells. Furthermore, gelatin zymography of the conditioned medium showed increased MMP activities in keratinocytes with reduced HAI-1 expression. Treating SPINT1 KO HaCaT cells with dehydroxymethylepoxyquinomicin (DHMEQ), a small molecule inhibitor of NF-κB, abrogated the upregulation of MMP9 and the gelatinolytic activity associated with MMP-9. These results suggest that HAI-1 may play a critical role in epidermal basement membrane integrity by regulating NF-κB activation-induced upregulation of MMP-9.
Competing Interests: Declarations. Conflict of interest: The authors declare that there are no conflicts of interest. Ethical approval: All experiments were approved by the Animal Care and Use Committee of the University of Miyazaki (2000-004).
(© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.)
Databáze: MEDLINE
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