ArticleHuman cell2024
Loss of hepatocyte growth factor activator inhibitor type 1 (HAI-1) upregulates MMP-9 expression and induces degradation of the epidermal basement membrane.
Article in Human cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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4 authors.
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Abstract
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.
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