Effects of mucopolysaccharide polysulphate on tight junction barrier in human epidermal keratinocytes

Abstract

Tight junctions (TJs) play important roles in epidermal barrier function and their dysfunction is involved in the pathogenesis of various skin diseases, including atopic dermatitis (AD). Mucopolysaccharide polysulphate (MPS) is the active ingredient of a moisturizing agent used to treat xerosis in patients with AD; however, its mechanism of action on TJ barrier function remains unclear. To elucidate the effects of MPS on TJs, adult human epidermal keratinocyte (HEKa) cells were exposed to MPS, subjected to Western blotting and quantitative PCR analyses for the investigation of TJ‐related factors. MPS treatment significantly increased the mRNA and protein expression of claudin‐1 (CLDN1) and zonula occludens‐1, and significantly increased transepithelial electrical resistance (TEER), which indicates TJ integrity. Conversely, the sulphated and non‐sulphated glycosaminoglycans, chondroitin sulphate and hyaluronic acid, respectively, had little effect on TEER or the expression of mRNAs or TJ‐related proteins. Interestingly, MPS treatment also inactivated the extracellular signal‐regulated kinase signalling pathway, which is known to negatively regulate CLDN1 expression. Furthermore, MPS notably improved the reduction in CLDN1 expression and TEER caused by histamine, which is upregulated in the skin of patients with AD and is known to disrupt the TJ barrier function. Taken together, these findings demonstrate that treatment with the moisturizing agent, MPS, can repair TJ dysfunction and could therefore represent a new therapeutic option for treating patients with AD.

The Effects of Mucopolysaccharide Polysulfate on Steroid-Induced Tight Junction Barrier Dysfunction in Human Epidermal Keratinocytes and a 3D Skin Model

“…This discrepancy may be because MPS also affects barrier function-related factors, like TJ-related proteins except for claudin-1 and differentiation markers, in keratinocytes. In our previous report [31], MPS increased the protein levels of claudin-1 and ZO-1, a TJ constituent, in normal HEKa. Wen et al [32] reported that topical MPS-containing products increased mRNA expressions of epidermal differentiation markers and lipid synthetic enzymes in clobetasol propionate-containing product-induced skin barrier impairment in mice.…”

“…The interaction of hyaluronic acid with its receptor CD44 has also been reported to inhibit CP-induced skin atrophy [29], and in the CD44 knockout keratinocytes, claudin-1 expression is reduced and TJ barrier formation is delayed [37]. Recently, it has been reported that MPS-containing creams suppress CP-induced skin atrophy in mice and show efficacy against CP-induced impairment of the epidermal permeability barrier [32] and that treatment of keratinocytes with MPS increases TJ-related proteins such as claudin-1 and ZO-1 [31]. In consideration of these reports, it is suggested that CD44 activation may be involved in the increased expression of TJ-related proteins in MPS, but the relationship with CD44 signaling needs to be examined in future studies.…”

mTOR signaling pathway regulation HIF-1 α effects on LPS induced intestinal mucosal epithelial model damage

“…FD−4 is a marker of changes in intestinal permeability and the intestinal barrier [ 23 ]. TJ-related proteins, including ZO−1, occludin, and claudin−1, play important roles in maintaining intercellular connections and cell barriers [ 24 , 25 ]. Occludin plays an important role in maintaining the intestinal TEER, has adhesion functions, and serves as a fence.…”

“…Claudin−1 affects the permeability of intercellular substances, especially cations, forming a selective paracellular ion channel. ZO−1 binds to a variety of cytoskeletal proteins and plays a supporting role in TJs [ 24 , 25 ].…”

Use of a Silkworm (Bombyx mori) Larvae By-Product for the Treatment of Atopic Dermatitis: Inhibition of NF-κB Nuclear Translocation and MAPK Signaling

“…Decreased claudin-1 protein expression is strongly associated with AD severity. Abnormal filaggrin expression is also prominent in patients with AD [ 6 ]. In addition to skin barrier dysfunction, the key role of Th2 cells in AD has been well documented in relation to the immune response.…”