Results for “Slc1a3”

PubMed2026

Skin-innervating glutamatergic neurons modulate aging.

Peripheral nerves regulate skin homeostasis by secreting neurotransmitters, but their role during skin aging remains incompletely understood. Here, we report that cutaneous denervation accelerates skin aging, as evidenced by collagen reduction. Neurofilament heavy chain (Nefh) is decreased in aged skin and is predominantly expressed in vesicular glutamate transporter 2-positive (Vglut2+) skin-innervating glutamatergic neurons. Notably, dermal fibroblasts, the primary producers of collagen, frequently contact Nefh+ nerve fibers. Moreover, Nefh deletion in Vglut2+ glutamatergic neurons drives skin fibroblast senescence and collagen loss, whereas additional glutamate improves skin aging phenotypes. Mechanistically, cyclin-dependent kinase 5 (Cdk5) interacts with both Nefh and Vglut2 and maintains glutamate release and collagen homeostasis. Additionally, in skin fibroblasts, solute carrier family 1 member 3 (Slc1a3) governs the collagen-promoting and anti-senescence functions of glutamate. Together, these findings reveal Nefh-mediated glutamatergic neuromodulation of skin aging and provide therapeutic targets for aging-related skin disorders.

Animals↗

PubMed2026

Multi-omics integration and colocalization analyses prioritize candidate molecular loci associated with hypothermia.

BACKGROUND: Hypothermia is a life-threatening condition lacking specific pharmacological treatments. This study aimed to prioritize genetically supported molecular loci associated with hypothermia and to explore their pharmacological tractability using multi-omics data. METHODS: Initially, 2532 druggable genes were curated from the Drug-Gene Interaction Database and established literature. These were cross-referenced with cis-eQTL and cis-pQTL datasets, encompassing 870,655 and 114,281 SNPs for blood, respectively, alongside 2379 shared SNPs across adipose, skeletal muscle, and heart tissues. Matched instrumental variables were integrated with hypothermia GWAS summary statistics for two-sample Mendelian randomization (MR) and Bayesian colocalization. Transcriptomic differential expression analysis (DEA) was subsequently conducted as an exploratory analysis of cold-exposure-associated expression changes. Database-derived compound annotations were systematically re-evaluated according to target specificity, established pharmacological mechanism, and concordance with the direction of the MR estimates. RESULTS: Among 671 gene-level MR tests, 36 genes reached nominal significance, whereas only ABCC8 remained significant after FDR correction. Colocalization was evaluable for 8 of these 36 genes, and 4 loci (COL18A1, SLC1A7, ADIPOQ, and MERTK) met the prespecified PP.H4>0.90 threshold. The remaining 28 loci were not evaluable because sufficient overlapping regional variants were unavailable after harmonization. Transcriptomic analysis identified altered expression of SLC1A3 and SLCO4A1 under cold exposure, although these findings did not directly validate the colocalization-supported loci. Re-evaluation of database-derived compound annotations did not identify any direct, selective, and directionally concordant drug-repurposing candidate for hypothermia. CONCLUSIONS: COL18A1, SLC1A7, ADIPOQ, and MERTK showed colocalization support among the 8 evaluable nominal MR-associated loci. Because colocalization coverage was limited, these genes should be regarded as preliminary candidate loci rather than established therapeutic targets. The pharmacological annotations were indirect, non-selective, unsupported, or directionally inconsistent and should be interpreted solely as hypothesis-generating information.

Bayesian colocalization↗