TY - JOUR

T1 - Organic osmolytes increase expression of specific tight junction proteins in skin and alter barrier function in keratinocytes

AU - El-Chami, C

AU - Foster, A R

AU - Johnson, C

AU - Clausen, R P

AU - Cornwell, P

AU - Haslam, I S

AU - Steward, M C

AU - Watson, R E B

AU - Young, H S

AU - O'Neill, C A

N1 - This article is protected by copyright. All rights reserved.

PY - 2021

Y1 - 2021

N2 - BACKGROUND: The epidermal barrier is important for water conservation, failure of which is evident in dry skin conditions. Barrier function is fulfilled by the stratum corneum, tight junctions (TJs; which control extracellular water) and keratinocyte mechanisms, such as organic osmolyte transport, which regulate intracellular water homeostasis. Organic osmolyte transport by keratinocytes is largely unexplored and nothing is known regarding how cellular and extracellular mechanisms of water conservation may interact.OBJECTIVE: We aimed to characterise osmolyte transporters in skin and keratinocytes, and using transporter inhibitors, to investigate whether osmolytes can modify TJs thus suggesting a possible link between intracellular and extracellular mechanisms of water regulation in skin.METHODS: Immunostaining and QPCR of organic osmolyte-treated organ cultured skin were used to identify changes to organic osmolyte transporter, and TJ protein and gene expression. TJ functional assays were performed on organic osmolyte-treated primary human keratinocytes in culture.RESULTS: Immunostaining demonstrated the expression of transporters for betaine, taurine and myo-inositol in transporter-specific patterns. Treatment of human skin with either betaine or taurine increased the expression of claudins-1, -4 and occludin. Osmolyte transporter inhibition abolished this response. Betaine and taurine increased TJ function in primary human keratinocytes in vitro.CONCLUSIONS: Treatment of skin with organic osmolytes modulates TJ structure and function, which could contribute to the epidermal barrier. This emphasises a role for organic osmolytes beyond the maintenance of intracellular osmolarity. This could be harnessed to enhance topical therapies for diseases characterised by skin barrier dysfunction.

AB - BACKGROUND: The epidermal barrier is important for water conservation, failure of which is evident in dry skin conditions. Barrier function is fulfilled by the stratum corneum, tight junctions (TJs; which control extracellular water) and keratinocyte mechanisms, such as organic osmolyte transport, which regulate intracellular water homeostasis. Organic osmolyte transport by keratinocytes is largely unexplored and nothing is known regarding how cellular and extracellular mechanisms of water conservation may interact.OBJECTIVE: We aimed to characterise osmolyte transporters in skin and keratinocytes, and using transporter inhibitors, to investigate whether osmolytes can modify TJs thus suggesting a possible link between intracellular and extracellular mechanisms of water regulation in skin.METHODS: Immunostaining and QPCR of organic osmolyte-treated organ cultured skin were used to identify changes to organic osmolyte transporter, and TJ protein and gene expression. TJ functional assays were performed on organic osmolyte-treated primary human keratinocytes in culture.RESULTS: Immunostaining demonstrated the expression of transporters for betaine, taurine and myo-inositol in transporter-specific patterns. Treatment of human skin with either betaine or taurine increased the expression of claudins-1, -4 and occludin. Osmolyte transporter inhibition abolished this response. Betaine and taurine increased TJ function in primary human keratinocytes in vitro.CONCLUSIONS: Treatment of skin with organic osmolytes modulates TJ structure and function, which could contribute to the epidermal barrier. This emphasises a role for organic osmolytes beyond the maintenance of intracellular osmolarity. This could be harnessed to enhance topical therapies for diseases characterised by skin barrier dysfunction.

U2 - 10.1111/bjd.19162

DO - 10.1111/bjd.19162

M3 - Journal article

C2 - 32348549

VL - 184

SP - 482

EP - 494

JO - British Journal of Dermatology

JF - British Journal of Dermatology

SN - 0007-0963

IS - 3

ER -