Ubiquitin-related Protein IFNGR1 as Causal Factor and Drug Target for Keloids: A Mendelian Randomization Analysis
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...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer
2025-08-01
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| Series: | Plastic and Reconstructive Surgery, Global Open |
| Online Access: | http://journals.lww.com/prsgo/fulltext/10.1097/GOX.0000000000007028 |
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| author | Yeltai Nurzat, PhD Zhenhe Guo, PhD Julong Hu, PhD Zaihuan Lin, MD Qi Zhang, PhD Gang Liang, MD Hang Ji, PhD, MD Xiaowen Zhang, PhD, MD |
| author_facet | Yeltai Nurzat, PhD Zhenhe Guo, PhD Julong Hu, PhD Zaihuan Lin, MD Qi Zhang, PhD Gang Liang, MD Hang Ji, PhD, MD Xiaowen Zhang, PhD, MD |
| author_sort | Yeltai Nurzat, PhD |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-23b208ba0f4a47439d2f434df7594fb8 |
| institution | Kabale University |
| issn | 2169-7574 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Plastic and Reconstructive Surgery, Global Open |
| spelling | doaj-art-23b208ba0f4a47439d2f434df7594fb82025-08-26T03:24:30ZengWolters KluwerPlastic and Reconstructive Surgery, Global Open2169-75742025-08-01138e702810.1097/GOX.0000000000007028202508000-00058Ubiquitin-related Protein IFNGR1 as Causal Factor and Drug Target for Keloids: A Mendelian Randomization AnalysisYeltai Nurzat, PhD0Zhenhe Guo, PhD1Julong Hu, PhD2Zaihuan Lin, MD3Qi Zhang, PhD4Gang Liang, MD5Hang Ji, PhD, MD6Xiaowen Zhang, PhD, MD7From 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† Department of Plastic Surgery, Southern Medical University Third Hospital, Guangzhou, Yuexiu, People’s Republic of ChinaFrom 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 ChinaFrom 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 ChinaFrom 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‡ Department of Plastic Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China‡ Department of Plastic Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaFrom 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 ChinaBackground:. 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.http://journals.lww.com/prsgo/fulltext/10.1097/GOX.0000000000007028 |
| spellingShingle | Yeltai Nurzat, PhD Zhenhe Guo, PhD Julong Hu, PhD Zaihuan Lin, MD Qi Zhang, PhD Gang Liang, MD Hang Ji, PhD, MD Xiaowen Zhang, PhD, MD Ubiquitin-related Protein IFNGR1 as Causal Factor and Drug Target for Keloids: A Mendelian Randomization Analysis Plastic and Reconstructive Surgery, Global Open |
| title | Ubiquitin-related Protein IFNGR1 as Causal Factor and Drug Target for Keloids: A Mendelian Randomization Analysis |
| title_full | Ubiquitin-related Protein IFNGR1 as Causal Factor and Drug Target for Keloids: A Mendelian Randomization Analysis |
| title_fullStr | Ubiquitin-related Protein IFNGR1 as Causal Factor and Drug Target for Keloids: A Mendelian Randomization Analysis |
| title_full_unstemmed | Ubiquitin-related Protein IFNGR1 as Causal Factor and Drug Target for Keloids: A Mendelian Randomization Analysis |
| title_short | Ubiquitin-related Protein IFNGR1 as Causal Factor and Drug Target for Keloids: A Mendelian Randomization Analysis |
| title_sort | ubiquitin related protein ifngr1 as causal factor and drug target for keloids a mendelian randomization analysis |
| url | http://journals.lww.com/prsgo/fulltext/10.1097/GOX.0000000000007028 |
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