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Updated: May 16, 2025

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice
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Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice

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Association and mediation between circulating inflammatory proteins and skin fibrosis

Zirui Zhao1, Dongming Lv2, Ruixi Zeng1

  • 1Department of Plastic Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.

Frontiers in Endocrinology
|April 2, 2025
PubMed
Abstract

Insights

This study used Mendelian randomization to find that circulating inflammatory proteins (CIPs) causally influence skin fibrosis. Blood metabolites like Vitamin A and cholesterol ratios mediate the effect of Fibroblast growth factor 21 on keloid formation.

Area of Science:

  • Dermatology
  • Genetics
  • Metabolomics

Background:

  • Skin fibrosis is a complex dermal condition linked to inflammation, but the precise causal role of circulating inflammatory proteins (CIPs) is not fully understood.
  • Investigating the interplay between CIPs, blood metabolites (BMs), and skin fibrosis is crucial for understanding disease mechanisms.

Purpose of the Study:

  • To elucidate the causal relationship between CIPs and skin fibrosis using Mendelian randomization (MR).
  • To explore the potential mediating role of BMs in the association between CIPs and skin fibrosis through two-step MR.

Main Methods:

  • Genome-wide association study (GWAS) summary statistics for CIPs, BMs, and skin fibrosis were utilized.
  • Two-sample MR and reverse MR analyses were performed to establish causality between CIPs and skin fibrosis, and between CIPs and BMs.
  • Two-step MR was employed to identify BMs mediating the effect of CIPs on skin fibrosis.

Main Results:

  • Bidirectional MR indicated inverse associations between skin fibrosis and T-cell surface glycoprotein CD6 isoform, Delta and Notch-like epidermal growth factor-related receptor, and Interleukin-10 receptor subunit beta.
  • A positive association was found between skin fibrosis and Fibroblast growth factor 21.
  • Two-step MR identified Retinol (Vitamin A) to linoleoyl-arachidonoyl-glycerol ratio and Cholesterol to linoleoyl-arachidonoyl-glycerol ratio as mediators for Fibroblast growth factor 21's effect on keloid formation.

Conclusions:

  • The study provides evidence for a causal link between specific CIPs and skin fibrosis.
  • Blood metabolites, particularly ratios involving Vitamin A and cholesterol, may mediate the impact of Fibroblast growth factor 21 on keloid development.
  • These findings suggest potential targets for early screening and preventative strategies for skin fibrosis.
Keywords:
bidirectional Mendelian randomizationblood metabolitecirculating inflammatory proteinmediation analysisskin fibrosis

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