International Heart Journal
Online ISSN : 1349-3299
Print ISSN : 1349-2365
ISSN-L : 1349-2365
Experimental Studies
Cell Cycle Perturbation Induces Collagen Production in Fibroblasts
Masaki WakeNorihiko TakedaTakayuki IsagawaTatsuyuki SatoYu NakagamaMasaki Suimye MoriokaYasushi HirotaMasataka AsagiriKoji MaemuraIchiro ManabeKazuaki TanabeIssei Komuro
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Supplementary material

2019 Volume 60 Issue 4 Pages 958-963


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.

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.

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© 2019 by the International Heart Journal Association
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