Advanced Glycation End Products Alter the M⁶A-Modified RNA Profiles in Human Dermal Fibroblasts

Abstract

Background: To explore advanced glycation end products (AGEs)-induced m⁶A modification in fibroblasts and its potential role in photoaging. Methods: We studied m⁶A modification in AGEs-bovine serum albumin-treated fibroblasts with m⁶A-mRNA & lncRNA epitranscriptomic microarray and bioinformatics analysis. The m⁶A modification level was also investigated in skin samples. Results: m⁶A methylation microarray analysis revealed m⁶A modification profiles in AGEs-treated fibroblasts. Gene ontology, Kyoto Encyclopedia of Genes and Genomes, protein–protein interaction and competing endogenous RNA network analysis indicated that the genes of differentially methylated mRNAs and lncRNAs were mainly related to inflammation processes. We also found that AGEs-bovine serum albumin dose-dependently increased the m⁶A level and METTL14 expression in both fibroblasts and sun-exposed skin. Conclusion: Our study provided novel information regarding alterations of m⁶A modifications in AGEs-induced dermal fibroblasts and potential targets for treatment of photoaging.

Keywords::

• advanced glycation end products
• bioinformatics analysis
• fibroblasts
• lncRNA
• m⁶A methylation
• photoaging
• skin

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2022-0016

Acknowledgments

The authors would like to especially thank M Wan and Y Xie for providing tissue samples obtained from donors in the Third Affiliated Hospital of Sun Yat-sen University.

Financial & competing interests disclosure

This work was supported by grants from National Natural Science Foundation of China (no. 81773340) and Natural Science Foundation of Guangdong Province (no. 2021A1515012622). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

Informed written consent of patients was obtained before all skin tissues resection and the consent procedure was conducted according to the principles expressed in the Declaration of Helsinki. All studies used were approved by the Ethical Committee of the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (no. [2014]2–64 and [2017]2–11).

Additional information

Funding

This work was supported by grants from National Natural Science Foundation of China (no. 81773340) and Natural Science Foundation of Guangdong Province (no. 2021A1515012622). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.