Lysophosphatidic acid regulates adhesion molecules and enhances migration of human oral keratinocytes

Abstract

Oral keratinocytes are connected via cell-to-cell adhesions to protect underlying tissues from physical and bacterial damage. Lysophosphatidic acids (LPAs) are a family of phospholipid mediators that have the ability to regulate gene expression, cytoskeletal rearrangement, and cytokine/chemokine secretion, which mediate proliferation, migration, and differentiation. Several forms of LPA are found in saliva and gingival crevicular fluid, but it is unknown how they affect human oral keratinocytes (HOK). The aim of the present study was therefore to examine how different LPA forms affect the expression of adhesion molecules and the migration and proliferation of HOK. Keratinocytes were isolated from gingival biopsies obtained from healthy donors and challenged with different forms of LPA. Quantitative real-time RT-PCR, immunocytochemistry, and flow cytometry were used to analyze the expression of adhesion molecules. Migration and proliferation assays were performed. Lysophosphatidic acids strongly promoted expression of E-cadherin and occludin mRNAs and translocation of E-cadherin protein from the cytoplasm to the membrane. Occludin and claudin-1 proteins were up-regulated by LPA. Migration of HOK in culture was increased, but proliferation was reduced, by the addition of LPA. This indicates that LPA can have a role in the regulation of the oral epithelial barrier by increasing the expression of adhesion molecules of HOK, by promotion of migration and by inhibition of proliferation.

Norway Spruce Balm: Phytochemical Composition and Ability to Enhance Re-epithelialization In Vitro

“…This suggests an additive or synergistic effect of these compounds. The presented data show that representatives of two compound classes, lignans (4) and diterpene resin acids (5)(6)(7)(8)(9)(10)(11), contribute to increased migration and proliferation of keratinocytes upon exposure to spruce balm. These findings are an initial step in the comprehensive and laborious process from a traditional natural product to a rational phytotherapeutic.…”

“…These concentrations were chosen as they did not markedly impede HaCaT viability in previous experiments (data not shown). As positive control, we used 10 µM LPA, a substance known to boost migration in different cell-types [11].…”

Deregulated expression of the 14q32 miRNA cluster in clear cell renal cancer cells

“…Since ccRCC is a metabolic disease that is characterized by changes in the lipidome ( 60 ), it is notable that we have uncovered alterations in the iron metabolic markers following cellular treatment with LPA, a potent lipid mitogen with roles in cancer pathogenesis ( 61 – 64 ). Specifically, we have demonstrated that LPA alters intracellular labile iron levels and expression of iron metabolic mediators in epithelial cells including FTSECs and RPTECs.…”