Age-related changes in cyclic phosphatidic acid-induced hyaluronic acid synthesis in human fibroblasts

Abstract

Hyaluronic acid is a major component of the extracellular matrix, which is important for skin hydration. As aging brings skin dehydration, we aimed to clarify the mRNA expression of hyaluronic acid-related proteins in human skin fibroblasts from donors of various ages (range 0.7-69 years). Previously, we reported that cyclic phosphatidic acid (cPA), a unique phospholipid mediator, stimulated the expression of HAS2 and increased hyaluronic acid synthesis in human skin fibroblasts (donor age: 3 days). In this study, we measured the mRNA expression of hyaluronic acid-related proteins: hyaluronan synthase (HAS) 1-3, hyaluronidase-1, -2, and hyaluronic acid-binding protein (versican). In addition, we tested whether cPA could increase hyaluronic acid synthesis in skin fibroblasts derived from donors of various ages. The expression of HAS1, 3, hyaluronidase-1, and -2 did not change with aging. However, the mRNA expression of versican decreased with aging. Although it is thought that the amount of hyaluronic acid in the dermis decreases with aging, the mRNA expression of HAS2 was increased. But the amount of hyaluronic acid secreted by fibroblasts did not increase with aging. This suggests that the activity and/or protein expression of HAS2 decrease with aging. Furthermore, we observed that cPA caused the increase of hyaluronic acid synthesis at any age, and this effect was increased with aging. These results suggest that aging made the fibroblasts more sensitive to cPA treatment. Therefore, cPA represents a suitable candidate for the health maintenance and improvement of the skin by increasing the level of hyaluronic acid in the dermis.

Synthesis and hydrolytic stability of cyclic phosphatidic acids: implications for synthetic- and proto-cell studies

“…[5][6][7] cPAs are also widespread in mammalian serum and brain tissues, and are known to play important roles in many biological functions. 8 Even though cyclic phosphatidic acids (cPAs) are generated by intramolecular transphosphatidylation of lysophosphatidylcholine (LPC) 9 and are structural analogs of LPA binding to the same receptors as LPA, cPAs exhibit unique activity and elicit completely different behavior than LPA, intensifying the scrutiny of the role of cPAs and its analogs as therapeutic (PPARg agonist or antagonistic properties) agents, 10,11 as candidates for increasing the level of hyaluronic acid in the dermis, 12 and as a novel pruritic agent. 13 The cPA bioactivity potential (regulation of cell proliferation, morphology and migration) is gaining attention 10,14 and their synthetic availability for medicinal and therapeutic investigations has become important.…”

Enhancement of Cornified Envelope-Related Gene and Protein Expression by Carba Cyclic Phosphatidic Acid in Normal Human Epidermal Keratinocytes

“…21) ccPA bind the same LPA receptor. 19,[22][23][24] Therefore, whether ccPA mediate the RHO-ROCK-SRF pathway as with LPA, and how much stronger their effects on keratinocyte differentiation are than that of LPA, should be examined in detail. ccPA may convert to LPA, which increases the mRNA levels of claudin 1 and occludin, two tight junction-forming proteins involved in barrier function.…”

“…By virtue of its increased stability, ccPA is reported to be more effective at inhibiting invasion by and metastasis of cancer cells than cPA. 19) In this study, we focused on stratum corneum barrier function in the CE and studied the effects of ccPA on CE formation and keratinocyte differentiation.…”

Fluoride Interferes with the Sperm Fertilizing Ability via Downregulated SPAM1, ACR, and PRSS21 Expression in Rat Epididymis

“…40 Hyaluronic acid was a major component of the extracellular matrix, and it was hydrolyzed by hyaluronidase into oligosaccharides. 41 SPAM1 was glycosylphosphatidylinositol anchored only on the plasma membrane of sperm and has hyaluronidase activity. 15 When the enzyme activity of SPAM1 was blocked, sperm were incapable of entering into the cumulus cell layer.…”

“…The egg cumulus cell layer was abundant in hyaluronic acid . Hyaluronic acid was a major component of the extracellular matrix, and it was hydrolyzed by hyaluronidase into oligosaccharides . SPAM1 was glycosylphosphatidylinositol anchored only on the plasma membrane of sperm and has hyaluronidase activity .…”