Loss of PARP-1 attenuates diabetic arteriosclerotic calcification via Stat1/Runx2 axis
| Autor: | Qing-hua Lu, Wen Qiao, Xue Liu, Ying Wang, Ming-Xiang Zhang, Peng Li, Fei Xie, Zhao-yang Wang, Bin Liu, Er-shun Liang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Vascular smooth muscle Immunology Macrophage polarization Poly (ADP-Ribose) Polymerase-1 Core Binding Factor Alpha 1 Subunit 030204 cardiovascular system & hematology Poly(ADP-ribose) Polymerase Inhibitors Article Muscle Smooth Vascular Calcification Diabetes Complications 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Apolipoproteins E Osteogenesis Diabetes mellitus Medicine Animals STAT1 lcsh:QH573-671 Promoter Regions Genetic Vascular Calcification Transcription factor Mice Knockout biology lcsh:Cytology business.industry Macrophages Correction Cell Biology Phenanthrenes medicine.disease Atherosclerosis Phenotype RUNX2 030104 developmental biology STAT1 Transcription Factor Differentiation Cancer research biology.protein business Protein Binding |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 11, Iss 1, Pp 1-13 (2020) |
| ISSN: | 2041-4889 |
| Popis: | Accelerated atherosclerotic calcification is responsible for plaque burden, especially in diabetes. The regulatory mechanism for atherosclerotic calcification in diabetes is poorly characterized. Here we show that deletion of PARP-1, a main enzyme in diverse metabolic complications, attenuates diabetic atherosclerotic calcification and decreases vessel stiffening in mice through Runx2 suppression. Specifically, PARP-1 deficiency reduces diabetic arteriosclerotic calcification by regulating Stat1-mediated synthetic phenotype switching of vascular smooth muscle cells and macrophage polarization. Meanwhile, both vascular smooth muscle cells and macrophages manifested osteogenic differentiation in osteogenic media, which was attenuated by PARP-1/Stat1 inhibition. Notably, Stat1 acts as a positive transcription factor by directly binding to the promoter of Runx2 and promoting atherosclerotic calcification in diabetes. Our results identify a new function of PARP-1, in which metabolism disturbance-related stimuli activate the Runx2 expression mediated by Stat1 transcription to facilitate diabetic arteriosclerotic calcification. PARP-1 inhibition may therefore represent a useful therapy for this challenging complication. |
| Databáze: | OpenAIRE |
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