Epigenetic Regulation Mediated by Methylation in the Pathogenesis and Precision Medicine of Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a complex disease triggered by the interaction between genetics and the environment, especially through the shared epitope (SE) and cell surface calreticulin (CSC) theory. However, the available evidence shows that genetic diversity and environmental exposure cannot expl...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-08-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2020.00811/full |
| _version_ | 1811225595631108096 |
|---|---|
| author | Shicheng Guo Shicheng Guo Lingxia Xu Lingxia Xu Cen Chang Cen Chang Runrun Zhang Runrun Zhang Yehua Jin Yehua Jin Dongyi He Dongyi He |
| author_facet | Shicheng Guo Shicheng Guo Lingxia Xu Lingxia Xu Cen Chang Cen Chang Runrun Zhang Runrun Zhang Yehua Jin Yehua Jin Dongyi He Dongyi He |
| author_sort | Shicheng Guo |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is a complex disease triggered by the interaction between genetics and the environment, especially through the shared epitope (SE) and cell surface calreticulin (CSC) theory. However, the available evidence shows that genetic diversity and environmental exposure cannot explain all the clinical characteristics and heterogeneity of RA. In contrast, recent studies demonstrate that epigenetics play important roles in the pathogenesis of RA, especially DNA methylation and histone modification. DNA methylation and histone methylation are involved in innate and adaptive immune cell differentiation and migration, proliferation, apoptosis, and mesenchymal characteristics of fibroblast-like synoviocytes (FLS). Epigenetic-mediated regulation of immune-related genes and inflammation pathways explains the dynamic expression network of RA. In this review, we summarize the comprehensive evidence to show that methylation of DNA and histones is significantly involved in the pathogenesis of RA and could be applied as a promising biomarker in the disease progression and drug-response prediction. We also explain the advantages and challenges of the current epigenetics research in RA. In summary, epigenetic modules provide a possible interface through which genetic and environmental risk factors connect to contribute to the susceptibility and pathogenesis of RA. Additionally, epigenetic regulators provide promising drug targets to develop novel therapeutic drugs for RA. Finally, DNA methylation and histone modifications could be important features for providing a better RA subtype identification to accelerate personalized treatment and precision medicine. |
| first_indexed | 2024-04-12T09:09:59Z |
| format | Article |
| id | doaj.art-034fdf7212724de28991e10276c93448 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-12T09:09:59Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-034fdf7212724de28991e10276c934482022-12-22T03:38:59ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-08-011110.3389/fgene.2020.00811552498Epigenetic Regulation Mediated by Methylation in the Pathogenesis and Precision Medicine of Rheumatoid ArthritisShicheng Guo0Shicheng Guo1Lingxia Xu2Lingxia Xu3Cen Chang4Cen Chang5Runrun Zhang6Runrun Zhang7Yehua Jin8Yehua Jin9Dongyi He10Dongyi He11Department of Medical Genetics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United StatesCenter for Precision Medicine Research, Marshfield Clinic Research Institute, Marshfield, WI, United StatesDepartment of Rheumatology, Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaRheumatoid arthritis (RA) is a complex disease triggered by the interaction between genetics and the environment, especially through the shared epitope (SE) and cell surface calreticulin (CSC) theory. However, the available evidence shows that genetic diversity and environmental exposure cannot explain all the clinical characteristics and heterogeneity of RA. In contrast, recent studies demonstrate that epigenetics play important roles in the pathogenesis of RA, especially DNA methylation and histone modification. DNA methylation and histone methylation are involved in innate and adaptive immune cell differentiation and migration, proliferation, apoptosis, and mesenchymal characteristics of fibroblast-like synoviocytes (FLS). Epigenetic-mediated regulation of immune-related genes and inflammation pathways explains the dynamic expression network of RA. In this review, we summarize the comprehensive evidence to show that methylation of DNA and histones is significantly involved in the pathogenesis of RA and could be applied as a promising biomarker in the disease progression and drug-response prediction. We also explain the advantages and challenges of the current epigenetics research in RA. In summary, epigenetic modules provide a possible interface through which genetic and environmental risk factors connect to contribute to the susceptibility and pathogenesis of RA. Additionally, epigenetic regulators provide promising drug targets to develop novel therapeutic drugs for RA. Finally, DNA methylation and histone modifications could be important features for providing a better RA subtype identification to accelerate personalized treatment and precision medicine.https://www.frontiersin.org/article/10.3389/fgene.2020.00811/fullepigeneticmethylationrheumatoid arthritispathogenesisregulation |
| spellingShingle | Shicheng Guo Shicheng Guo Lingxia Xu Lingxia Xu Cen Chang Cen Chang Runrun Zhang Runrun Zhang Yehua Jin Yehua Jin Dongyi He Dongyi He Epigenetic Regulation Mediated by Methylation in the Pathogenesis and Precision Medicine of Rheumatoid Arthritis Frontiers in Genetics epigenetic methylation rheumatoid arthritis pathogenesis regulation |
| title | Epigenetic Regulation Mediated by Methylation in the Pathogenesis and Precision Medicine of Rheumatoid Arthritis |
| title_full | Epigenetic Regulation Mediated by Methylation in the Pathogenesis and Precision Medicine of Rheumatoid Arthritis |
| title_fullStr | Epigenetic Regulation Mediated by Methylation in the Pathogenesis and Precision Medicine of Rheumatoid Arthritis |
| title_full_unstemmed | Epigenetic Regulation Mediated by Methylation in the Pathogenesis and Precision Medicine of Rheumatoid Arthritis |
| title_short | Epigenetic Regulation Mediated by Methylation in the Pathogenesis and Precision Medicine of Rheumatoid Arthritis |
| title_sort | epigenetic regulation mediated by methylation in the pathogenesis and precision medicine of rheumatoid arthritis |
| topic | epigenetic methylation rheumatoid arthritis pathogenesis regulation |
| url | https://www.frontiersin.org/article/10.3389/fgene.2020.00811/full |
| work_keys_str_mv | AT shichengguo epigeneticregulationmediatedbymethylationinthepathogenesisandprecisionmedicineofrheumatoidarthritis AT shichengguo epigeneticregulationmediatedbymethylationinthepathogenesisandprecisionmedicineofrheumatoidarthritis AT lingxiaxu epigeneticregulationmediatedbymethylationinthepathogenesisandprecisionmedicineofrheumatoidarthritis AT lingxiaxu epigeneticregulationmediatedbymethylationinthepathogenesisandprecisionmedicineofrheumatoidarthritis AT cenchang epigeneticregulationmediatedbymethylationinthepathogenesisandprecisionmedicineofrheumatoidarthritis AT cenchang epigeneticregulationmediatedbymethylationinthepathogenesisandprecisionmedicineofrheumatoidarthritis AT runrunzhang epigeneticregulationmediatedbymethylationinthepathogenesisandprecisionmedicineofrheumatoidarthritis AT runrunzhang epigeneticregulationmediatedbymethylationinthepathogenesisandprecisionmedicineofrheumatoidarthritis AT yehuajin epigeneticregulationmediatedbymethylationinthepathogenesisandprecisionmedicineofrheumatoidarthritis AT yehuajin epigeneticregulationmediatedbymethylationinthepathogenesisandprecisionmedicineofrheumatoidarthritis AT dongyihe epigeneticregulationmediatedbymethylationinthepathogenesisandprecisionmedicineofrheumatoidarthritis AT dongyihe epigeneticregulationmediatedbymethylationinthepathogenesisandprecisionmedicineofrheumatoidarthritis |