Protein malnutrition impairs skin elasticity in hairless mice by downregulating tropoelastin, fibrillin-1, and lysyl oxidase-like protein-1

Malnutrition is a known cause of skin disorders, but the genetic mechanisms linking it to dermal dysfunctions, particularly skin elasticity, are not fully understood. This study aimed to investigate how protein malnutrition (PM) affects the structure of the skin by reducing elastic fiber components and to examine the underlying genetic mechanisms. We used a non-invasive skin pinch test to assess skin elasticity and conducted gene expression analysis. Mice were divided into a control group (20% casein diet) and a PM group (2% casein diet) and were fed for 28 days. Skin elasticity, histopathological changes, plasma biochemical parameters, and insoluble α-elastin levels were measured. Quantitative Polymerase Chain Reaction (qPCR) was used to analyze the expression of genes related to elastic fiber metabolism, including matrix metalloproteinases (MMPs), lysyl oxidase-like protein 1 (LOXL1), tropoelastin, and fibrillin-1. Skin elasticity in the PM group was significantly impaired by day 7 and worsened until day 28. Histologically, PM induced epidermal thinning and dermal loosening by day 7, which persisted throughout the study. The elastic fibers content significantly decreased in the PM group by day 28. Gene expression analysis revealed that lysyl oxidase-like protein 1 (LOXL1), tropoelastin, and fibrillin-1 were significantly downregulated in the PM group. MMP expression showed minimal changes. These findings suggest that the observed skin structural defects and impaired skin elasticity under PM conditions are primarily caused by a substantial reduction in elastic fibers due to insufficient elastogenesis, rather than increased degradation.