Evidence map›Paper›PMID 40827246›Full record

ArticlePlastic and reconstructive surgery. Global open2025

Ubiquitin-related Protein IFNGR1 as Causal Factor and Drug Target for Keloids: A Mendelian Randomization Analysis.

Yeltai Nurzat, Zhenhe Guo, Julong Hu, Zaihuan Lin, Qi Zhang, Gang Liang, Hang Ji, Xiaowen Zhang

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Article in Plastic and reconstructive surgery. Global open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

8 authors.

Yeltai NurzatFrom the State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
Zhenhe GuoDepartment of Plastic Surgery, Southern Medical University Third Hospital, Guangzhou, Yuexiu, People's Republic of China.
Julong HuFrom the State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
Zaihuan LinFrom the State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
Qi ZhangFrom the State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
Gang LiangDepartment of Plastic Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
Hang JiDepartment of Plastic Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
Xiaowen ZhangFrom the State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Keloids, benign skin tumors due to connective tissue overgrowth, can be exacerbated by ubiquitin-proteasome system abnormalities through uncontrolled inflammation. This study aimed to use Mendelian randomization (MR) analysis to explore keloid pathogenesis and identify target drugs for treatment. Methods: The single-nucleotide polymorphism identifiers of keloid were obtained from the Open Genome-Wide Association Study database, and ubiquitin-related genes from GeneCards database. Five techniques were used for MR analysis during the research, with the accuracy of MR results evaluated by sensitivity analysis. Then, the R software package coloc was used for colocalization analysis of ubiquitin-related genes and keloid. Subsequently, the Comparative Toxicogenomics Database was used to predict skin complications related to keloid-associated target genes. Also, the Drug-Gene Interaction Database was used to study potential target drugs for target genes, and the mechanism of drug inhibition of keloid formation was explored using the DrugBank, Therapeutic Target Database, and STRING databases. Results: IFNGR1 and RNF187 were significant risk factors for keloid formation. A causal relationship exists between IFNGR1 and chronic skin ulcers (a keloid complication). Moreover, indole-3-carbinol, interferon gamma-1b, and pretomanid (targeting IFNGR1) are potential keloid treatments. Tretinoin can affect the IFNGR1 protein via the AKT1 pathway, inhibiting keloid proliferation. Conclusions: IFNGR1 was associated with the pathogenesis of keloids. Interferon gamma-1b targeting IFNGR1 might be a potential strategy for the treatment of keloids, and this discovery opened up a new direction for the treatment of keloids.

Identifiers

PMID40827246
PMCPMC12356637

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.