763 Novel roles of laminin α3 in epidermal homeostasis
نویسندگان
چکیده
The skin serves an important barrier function performed by epidermal lipids, cornified epithelial cells and cell-cell adhesions. This is compromised in old age exhibits abnormalities such as flattened dermal-epidermal junction or improper lipid metabolism also associated with mitochondrial dysfunction. A basement membrane protein laminin (LM)-332 known to be decreased skin. We have previously demonstrated that the loss of LM-332 leads upregulation cholesterol biosynthesis genes altered skin’s profile. showed this change caused abnormal actin-dependent intracellular transport. To further elucidate mechanism controlling transport, we developed 2D 3D models grown using control α3 subunit knockdown nTERT keratinocytes. used proteomic, lipidomic, transcriptomic analyses investigate changes these models. identified statistically significant actin linked vesicular transport networks, cell adhesion tissue differentiation well unexpected metabolic loss. Western Blot analysis two proteins involved NPC2 myo5b are Interestingly, binding partner, NPC1, was increased knockdown. Our has a downregulation e-cadherin, α3. recovery experiments addition recombinant restores proper levels e-cadherin suggesting potential therapeutic effect. These findings show plays numerous, unreported roles adhesion, suggests role aging.
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ژورنال
عنوان ژورنال: Journal of Investigative Dermatology
سال: 2023
ISSN: ['1523-1747', '0022-202X']
DOI: https://doi.org/10.1016/j.jid.2023.03.772