Role of organic osmolytes in water homoeostasis in skin

Abstract

The ability to conserve water is fundamental to terrestrial life. A number of organs such as the kidney and the bladder have important roles in the regulation of body water balance. The epidermis of skin is also fundamental to this process, and it is in a constant battle to prevent loss of water to the external, dry environment. Given this important role of the epidermis as a barrier to water loss, it is perhaps surprising that many of the cellular mechanisms by which human keratinocytes achieve cell volume homoeostasis, maintain epidermal hydration and adapt to biological effects from environmental stressors such as ultraviolet radiation are poorly understood. This article reviews what is known thus far and speculates about other potential mechanisms through which skin conducts water homoeostasis, with a particular emphasis on the putative role of organic osmolytes.

Hypotonic stress response of human keratinocytes involves LRRC8A as component of volume‐regulated anion channels

“…First evidence has been provided that not only one particular, but rather several LRRC8 complexes composed of different subunits can exist within the same cell, which led to the hypothesis that distinct LRRC8 complexes serve to transport different organic osmolytes within the same cell . In keratinocytes, taurine and other organic osmolytes such as betaine and myo‐inositol play an important role not only in maintaining cell volume homoeostasis but also in protection from UV light . Exposure of cultivated keratinocytes to UV light or hypertonic stress stimulated organic osmolyte uptake, which reduced osmotically and UV‐induced apoptosis .…”

“…[39] In keratinocytes, taurine and other organic osmolytes such as betaine and myo-inositol play an important role not only in maintaining cell volume homoeostasis but also in protection from UV light. [1] Exposure of cultivated keratinocytes to UV light or hypertonic stress stimulated organic osmolyte uptake, which reduced osmotically and UV-induced apoptosis. [2,40] Conversely, hypotonic stress triggered efflux of organic osmolytes.…”

“…The human epidermis not only forms an important barrier against detrimental environmental influences, but it also plays a fundamental role in water homoeostasis of the skin: It contributes to maintaining the hydration state of the body by preventing transepidermal water loss and protects against environmental osmotic fluctuations . However, when barrier function is impaired, the underlying epidermal keratinocytes become a direct target to osmotic stress .…”

“…The human epidermis not only forms an important barrier against detrimental environmental influences, but it also plays a fundamental role in water homoeostasis of the skin: It contributes to maintaining the hydration state of the body by preventing transepidermal water loss and protects against environmental osmotic fluctuations. [1] However, when barrier function is impaired, the underlying epidermal keratinocytes become a direct target to osmotic stress. [2] Clinically, it is well known that dry skin and disorders related to disturbed barrier function such as psoriasis or atopic dermatitis can be aggravated by hypertonic as well as hypotonic osmotic stress originating from exposure to low humidity and freshwater, respectively.…”

“…[7,8] Volume-regulated anion channels play a central role during RVD in many mammalian tissues; however, their role during hypotonic stress response in the human epidermis is only partially understood. [1] It is well established that primary normal human epidermal keratinocytes (NHEKs) and the immortalized HaCaT keratinocyte cell line respond to hypotonic stimulation by eliciting Cl − currents that are characteristic for VRACs and similar to those observed in other cell types. [9][10][11] In addition, NHEKs can release organic osmolytes in response to hypotonic stress.…”