The m 6 A-methylated mRNA pattern and the activation of the Wnt signaling pathway under the hyper-m 6 A-modifying condition in the keloid.

Autor:	Lin CX; Key Laboratory of Regenerative Medicine, Ministry of Education, Department of Plastic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China., Chen ZJ; Key Laboratory of Regenerative Medicine, Ministry of Education, Department of Plastic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China., Peng QL; The Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China., Xiang KR; Key Laboratory of Regenerative Medicine, Ministry of Education, Department of Plastic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China., Xiao DQ; Department of Thoracic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China., Chen RX; Key Laboratory of Regenerative Medicine, Ministry of Education, Department of Plastic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China., Cui T; Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC, United States., Huang YS; Department of Wound Repair, Institute of Wound Repair and Regeneration Medicine, Southern University of Science and Technology Hospital, Southern University of Science and Technology School of Medicine, Shenzhen, China., Liu HW; Key Laboratory of Regenerative Medicine, Ministry of Education, Department of Plastic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Jazyk:	angličtina
Zdroj:	Frontiers in cell and developmental biology [Front Cell Dev Biol] 2022 Oct 03; Vol. 10, pp. 947337. Date of Electronic Publication: 2022 Oct 03 (Print Publication: 2022).
DOI:	10.3389/fcell.2022.947337
Abstrakt:	Purpose: The present study was carried out to investigate the global m 6 A-modified RNA pattern and possible mechanisms underlying the pathogenesis of keloid. Method: In total, 14 normal skin and 14 keloid tissue samples were first collected on clinics. Then, three samples from each group were randomly selected to be verified with the Western blotting to determine the level of methyltransferase and demethylase. The total RNA of all samples in each group was isolated and subjected to the analysis of MeRIP sequencing and RNA sequencing. Using software of MeTDiff and htseq- count, the m 6 A peaks and differentially expressed genes (DEGs) were determined within the fold change >2 and p- value < 0.05. The top 10 pathways of m 6 A-modified genes in each group and the differentially expressed genes were enriched by the Kyoto Encyclopedia of Genes and Genomes signaling pathways. Finally, the closely associated pathway was determined using the Western blotting and immunofluorescence staining. Results: There was a higher protein level of WTAP and Mettl3 in the keloid than in the normal tissue. In the keloid samples, 21,020 unique m 6 A peaks with 6,573 unique m 6 A-associated genetic transcripts appeared. In the normal tissue, 4,028 unique m 6 A peaks with 779 m 6 A-associated modified genes appeared. In the RNA sequencing, there were 847 genes significantly changed between these groups, transcriptionally. The genes with m 6 A-methylated modification and the upregulated differentially expressed genes between two tissues were both mainly related to the Wnt signaling pathway. Moreover, the hyper-m 6 A-modified Wnt/ β -catenin pathway in keloid was verified with Western blotting. From the immunofluorescence staining results, we found that the accumulated fibroblasts were under a hyper-m 6 A condition in the keloid, and the Wnt/ β -Catenin signaling pathway was mainly activated in the fibroblasts. Conclusion: The fibroblasts in the keloid were under a cellular hyper-m 6 A-methylated condition, and the hyper-m 6 A-modified highly expressed Wnt/ β -catenin pathway in the dermal fibroblasts might promote the pathogenesis of keloid. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Lin, Chen, Peng, Xiang, Xiao, Chen, Cui, Huang and Liu.)
Databáze:	MEDLINE
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