Cell Cycle Perturbation Induces Collagen Production in Fibroblasts
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- Wake Masaki
- Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo Department of Cardiology, Shimane University Faculty of Medicine
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- Takeda Norihiko
- Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo
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- Isagawa Takayuki
- Graduate School of Biomedical Science, Nagasaki University
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- Sato Tatsuyuki
- Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo
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- Nakagama Yu
- Department of Pediatrics, Graduate School of Medicine, The University of Tokyo
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- Morioka Masaki Suimye
- Department of Bioinformatics, Medical Research Institute, Tokyo Medical and Dental University
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- Hirota Yasushi
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo
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- Asagiri Masataka
- Department of Pathobiology, Graduate School of Pharmaceutical Sciences, Nagoya City University
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- Maemura Koji
- Graduate School of Biomedical Science, Nagasaki University
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- Manabe Ichiro
- Department of Disease Biology and Molecular Medicine, Graduate School of Medicine, Chiba University
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- Tanabe Kazuaki
- Department of Cardiology, Shimane University Faculty of Medicine
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- Komuro Issei
- Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo
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Abstract
<p>Myocardial infarction (MI) occurs when the heart muscle is severely damaged due to a decrease in blood flow from the coronary arteries. During recovery from an MI, cardiac fibroblasts become activated and produce extracellular matrices, contributing to the wound healing process in the damaged heart. Inappropriate activation of the fibroblasts leads to excessive fibrosis in the heart. However, the molecular pathways by which cardiac fibroblasts are activated have not yet been fully elucidated.</p><p>Here we show that serum deprivation, which recapitulates the cellular microenvironment of the MI area, strikingly induces collagen production in C3H/10T1/2 cells. Based on transcriptomic and pharmacological studies, we found that cell cycle perturbation is directly linked to collagen production in fibroblasts. Importantly, collagen synthesis is increased independently of the transcriptional levels of type I collagen genes. These results reveal a novel mode of fibroblast activation in the ischemic area, which will allow us to gain insights into the molecular mechanisms underlying cardiac fibrosis and establish a basis for anti-fibrotic therapy.</p>
Journal
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- International Heart Journal
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International Heart Journal 60 (4), 958-963, 2019-07-30
International Heart Journal Association
