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Related Experiment Video

Updated: Jun 25, 2025

Isolation, Culture, and Characterization of Primary Dermal Fibroblasts from Human Keloid Tissue
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Identifying Potential Drug Targets for Keloid: A Mendelian Randomization Study.

Yinmin Wang1, Xiuxia Wang1, Zhaoqi Yuan1

  • 1Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The Journal of Investigative Dermatology
|May 26, 2024
PubMed
Summary

Identifying new drug targets for keloids is crucial. This study used Mendelian randomization to find seven potential protein targets, with neurotrimin (NTM) showing particular promise for keloid treatment.

Keywords:
Drug targetsFibroblastKeloidMendelian randomization studySkin fibrosis

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Area of Science:

  • Dermatology
  • Genetics
  • Pharmacology

Background:

  • Keloids are a challenging skin fibrosis condition with high recurrence and treatment side effects.
  • Effective keloid treatments necessitate the identification of novel drug targets.

Purpose of the Study:

  • To identify and validate potential protein drug targets for keloid treatment using a robust genetic approach.
  • To investigate the correlation and expression patterns of candidate proteins in keloid tissue.

Main Methods:

  • A two-sample Mendelian randomization analysis was performed using proteomic and keloid GWAS data.
  • Summary data-based Mendelian randomization and colocalization analyses were used to assess causality and distinguish linkage from pleiotropy.
  • Candidate targets were validated using single-cell RNA-sequencing, Western Blot, and immunofluorescence staining.

Main Results:

  • Seven proteins were identified as potential keloid drug targets.
  • Hedgehog-interacting protein, neurotrimin (NTM), KLKB1, and CRIPTO showed positive correlations with keloids.
  • PLXNC1, SCG3, and PDGFD showed negative correlations; NTM, PLXNC1, and PDGFD were highly expressed in fibroblasts, with NTM significantly increased in keloids.

Conclusions:

  • Neurotrimin (NTM), PLXNC1, and PDGFD are promising drug targets due to their fibroblast expression and correlation with keloid phenotypes.
  • NTM, in particular, demonstrates significant upregulation in keloids, suggesting its high therapeutic potential.
  • The identified proteins offer novel avenues for developing more effective keloid treatments.