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In Vitro Model of Human Cutaneous Hypertrophic Scarring using Macromolecular Crowding
Published on: May 1, 2020
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Causal correlation between inflammatory cytokines and hypertrophic scar based on two-sample Mendelian randomization
Lujia Mao1, Juan Huang2, Yixun Zhang3
1The Second Affiliated Hospital, School of Medicine, South China University of Technology, China; Department of Burn and Plastic Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
Journal, Genetic Engineering & Biotechnology
|December 12, 2025
Summary
Two inflammatory cytokines, IL-2 and CCL4, show a causal link to hypertrophic scars (HS). IL-2 increases HS risk, while CCL4 may protect against scar formation, impacting fibroblast activity and collagen levels.
Area of Science:
- Dermatology
- Immunology
- Genetics
Background:
- Hypertrophic scars (HS) arise from abnormal fibroblast proliferation and collagen accumulation post-skin injury.
- Inflammatory cytokines are key regulators, aberrantly activating fibroblasts, promoting collagen synthesis, and inhibiting degradation.
Purpose of the Study:
- To investigate the causal relationship between specific inflammatory cytokines and the development of hypertrophic scars.
- To determine if IL-2 and CCL4 play a direct role in hypertrophic scar pathogenesis.
Main Methods:
- Employed a two-sample Mendelian randomization (TSMR) approach using genome-wide association study (GWAS) data.
- Analyzed summarized data for inflammatory cytokines (8,293 samples) and hypertrophic scars (207,482 samples).
- Utilized inverse variance-weighted (IVW) method for causal analysis, alongside sensitivity, heterogeneity, and pleiotropy analyses.
Main Results:
- Identified a significant positive causal association between IL-2 and hypertrophic scar risk (OR = 1.51, P = 0.02).
- Found a significant negative causal association between CCL4 and hypertrophic scar risk (OR = 0.86, P = 0.03).
- Sensitivity analyses confirmed the robustness and reliability of the TSMR findings.
Conclusions:
- Demonstrated a causal correlation between inflammatory cytokines and hypertrophic scars.
- IL-2 acts as a risk factor promoting hypertrophic scar formation.
- CCL4 appears to have a protective effect, potentially inhibiting scar formation.
