Rosiglitazone reduces diabetes angiopathy by inhibiting mitochondrial dysfunction dependent on regulating HSP22 expression
Summary: The effects of rosiglitazone (RSG) in patients with type 2 diabetes mellitus (T2DM) remain controversial. Here, we first used network pharmacology to identify the common targets of RSG in the treatment of diabetes angiopathy (DA). Enrichment analysis found that the common genes were involve...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223002717 |
| _version_ | 1797867620277420032 |
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| author | Lingling Yu Shengsong Chen Qian Liang Chahua Huang Weifang Zhang Longlong Hu Yun Yu Liang Liu Xiaoshu Cheng Huihui Bao |
| author_facet | Lingling Yu Shengsong Chen Qian Liang Chahua Huang Weifang Zhang Longlong Hu Yun Yu Liang Liu Xiaoshu Cheng Huihui Bao |
| author_sort | Lingling Yu |
| collection | DOAJ |
| description | Summary: The effects of rosiglitazone (RSG) in patients with type 2 diabetes mellitus (T2DM) remain controversial. Here, we first used network pharmacology to identify the common targets of RSG in the treatment of diabetes angiopathy (DA). Enrichment analysis found that the common genes were involved in the inflammatory response, leukocyte cell-cell adhesion, mitochondrion organization and oxidative stress. Our previous research confirmed that heat shock protein 22 (HSP22) suppresses diabetes-induced endothelial activation and injury by inhibiting mitochondrial reactive oxygen species (mtROS) formation and dysfunction. We then constructed HSP22 knockout mice with T2DM to investigate whether RSG protected the vascular endothelium by upregulating HSP22. Our study suggested that RSG reduced vascular endothelial cell activation and injury by decreasing monocyte adhesion and cytokine secretion and simultaneously upregulating HSP22 expression. Mechanistically, RSG inhibited mitochondrial oxidative stress and dysfunction by regulating PPAR-γ in a manner partially dependent on expression of HSP22, resulting in reduced DA. |
| first_indexed | 2024-04-09T23:43:03Z |
| format | Article |
| id | doaj.art-c3f63f8df01d4bcda24579238862c53e |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-09T23:43:03Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-c3f63f8df01d4bcda24579238862c53e2023-03-18T04:42:31ZengElsevieriScience2589-00422023-04-01264106194Rosiglitazone reduces diabetes angiopathy by inhibiting mitochondrial dysfunction dependent on regulating HSP22 expressionLingling Yu0Shengsong Chen1Qian Liang2Chahua Huang3Weifang Zhang4Longlong Hu5Yun Yu6Liang Liu7Xiaoshu Cheng8Huihui Bao9Department of Rehabilitation, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China; Department of Cardiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaDepartment of Pulmonary and Critical Care Medicine, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang 330006, ChinaDepartment of Public Health, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaDepartment of Cardiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaDepartment of Pharmacy, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaDepartment of Cardiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaDepartment of Cardiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaDepartment of Cardiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaDepartment of Cardiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China; Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang 330006, China; Jiangxi Sub-center of National Clinical Research Center for Cardiovascular Diseases, Nanchang 330006, China; Corresponding authorDepartment of Cardiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China; Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang 330006, China; Jiangxi Sub-center of National Clinical Research Center for Cardiovascular Diseases, Nanchang 330006, China; Corresponding authorSummary: The effects of rosiglitazone (RSG) in patients with type 2 diabetes mellitus (T2DM) remain controversial. Here, we first used network pharmacology to identify the common targets of RSG in the treatment of diabetes angiopathy (DA). Enrichment analysis found that the common genes were involved in the inflammatory response, leukocyte cell-cell adhesion, mitochondrion organization and oxidative stress. Our previous research confirmed that heat shock protein 22 (HSP22) suppresses diabetes-induced endothelial activation and injury by inhibiting mitochondrial reactive oxygen species (mtROS) formation and dysfunction. We then constructed HSP22 knockout mice with T2DM to investigate whether RSG protected the vascular endothelium by upregulating HSP22. Our study suggested that RSG reduced vascular endothelial cell activation and injury by decreasing monocyte adhesion and cytokine secretion and simultaneously upregulating HSP22 expression. Mechanistically, RSG inhibited mitochondrial oxidative stress and dysfunction by regulating PPAR-γ in a manner partially dependent on expression of HSP22, resulting in reduced DA.http://www.sciencedirect.com/science/article/pii/S2589004223002717DrugsHuman metabolism |
| spellingShingle | Lingling Yu Shengsong Chen Qian Liang Chahua Huang Weifang Zhang Longlong Hu Yun Yu Liang Liu Xiaoshu Cheng Huihui Bao Rosiglitazone reduces diabetes angiopathy by inhibiting mitochondrial dysfunction dependent on regulating HSP22 expression iScience Drugs Human metabolism |
| title | Rosiglitazone reduces diabetes angiopathy by inhibiting mitochondrial dysfunction dependent on regulating HSP22 expression |
| title_full | Rosiglitazone reduces diabetes angiopathy by inhibiting mitochondrial dysfunction dependent on regulating HSP22 expression |
| title_fullStr | Rosiglitazone reduces diabetes angiopathy by inhibiting mitochondrial dysfunction dependent on regulating HSP22 expression |
| title_full_unstemmed | Rosiglitazone reduces diabetes angiopathy by inhibiting mitochondrial dysfunction dependent on regulating HSP22 expression |
| title_short | Rosiglitazone reduces diabetes angiopathy by inhibiting mitochondrial dysfunction dependent on regulating HSP22 expression |
| title_sort | rosiglitazone reduces diabetes angiopathy by inhibiting mitochondrial dysfunction dependent on regulating hsp22 expression |
| topic | Drugs Human metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223002717 |
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