Role of NHE1 for skin acidity and barrier function = Role of NHE1 for skin acidity and barrier function

다국어 초록 (Multilingual Abstract)

The skin barrier consists of the stratum corneum (SC) and tight junctions, with skin surface pH, typically ranging from 4.5 to 5.5, playing a critical role in various aspects of robust skin barrier function. Skin barrier function relies on a delicate balance of SC intercellular lipids, natural moisturizing factors (NMFs), and acidity. Disruptions in any of these components can lead to barrier dysfunction, resulting in dryness, irritation, and various skin ailments. Increased skin pH and basal transepidermal water loss (TEWL), compromised SC integrity, reduced skin hydration, and elevated serine protease (SP) activity are all correlated with shifts in skin acidity. Skin pH is influenced by both intrinsic and extrinsic factors. Preserving mildly acidic pH at the skin surface is imperative for a healthy skin barrier. Elevated SC pH is linked with various skin conditions, including neonatal skin, aged skin, and inflammatory skin conditions like atopic dermatitis (AD). AD exhibits elevated skin surface pH, especially in the early stages, correlating with disease severity. Maintaining an acidic environment, such as bathing in acidic hot spring water or using acidic topical treatments, can alleviate symptoms in AD patients and reduce Staphylococcus aureus levels. Initial research on the role of sodium-proton exchanger 1 (NHE1) in skin barrier function found that depleting or inhibiting the NHE1 gene elevates SC pH, impeding lipid processing and skin barrier recovery. The study also examined neonatal skin, uncovering a gradual shift from a near-neutral pH at birth to an adult-like acidic state over several months, attributed to NHE1 activation and the involvement of enzymes such as secretory phospholipase A2. Elevated pH during a specific neonatal period delays skin barrier recovery due to the activation of enzymes like SP. Aged skin is often susceptible to inflammatory skin conditions, dryness, and eczema, which can be exacerbated by impaired epidermal barrier homeostasis. Recent research has revealed that in moderately aged skin, the main culprit for barrier issues is a deficiency in SC acidity due to reduced expression of the NHE1. Additionally, in moderately aged skin, decreased NHE1 levels lead to elevated SC pH, resulting in defective lipid processing and delayed formation of lipid membranes. These abnormalities can be rectified by acidifying the SC, forming the basis for acidification therapies widely used to treat pathological dryness and eczema in moderately aged individuals.