Neurotrimin Identified as Key Target for Keloid Treatment: Analysis

Key Takeaways

• Seven proteins were identified as potential drug targets for keloids, with neurotrimin (NTM) singled out for its significant role.
• Single-cell RNA sequencing showed high NTM expression in fibroblasts, particularly in keloids vs. normal scars.
• Validation experiments confirmed elevated NTM protein levels in keloid tissues.

Researchers for a new genetic study have identified seven proteins as potential drug targets for the treatment of keloids, with neurotrimin (NTM) emerging as a particularly significant finding.

Publishing in the Journal of Investigative Dermatology, the study design employed a two-sample Mendelian randomization (MR) analysis to identify proteins associated with keloids using data from the deCODE database and druggable genome resources. The proteins were evaluated through genetic correlation with keloids using a genome-wide association study (GWAS).  A colocalization analysis distinguished pleiotropy and linkage, and findings were validated with single-cell RNA sequencing, Western blot, and immunofluorescence techniques.

According to the analysis, the authors identified four proteins positively correlated with keloids—Hedgehog-interacting protein, neurotrimin (NTM), KLKB1, and CRIPTO—and three negatively correlated proteins (PLXNC1, SCG3, and PDGFD). Neurotrimin (NTM) was identified as a critical candidate for targeting. Single-cell RNA sequencing data showed NTM was highly expressed in fibroblasts, with significant overexpression in keloids vs. normal scars.

"Our findings indicated that NTM, PLXNC1, and PDGFD were highly expressed in the fibroblast group, with NTM exhibiting increased expression in the mesenchymal fibroblast subpopulation, particularly in keloid compared with that in normal scar tissue," the authors concluded. "Furthermore, the protein expression of NTM was higher in keloid samples than in normal skin. These results further support the potential of these proteins as reliable targets for keloid treatment, especially NTM."

Source:  Wang Y, et al. Journal of Investigative Dermatology.  2024. Doi:10.1016/j.jid.2024.04.023