IMR Press / FBL / Volume 22 / Issue 4 / DOI: 10.2741/4502

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

Implication of CD38 gene in autophagic degradation of collagen I in mouse coronary arterial myocytes

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1 Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA, 23298, USA
2 Department of Molecular Biology, University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany

Academic Editor: Xiao-Feng Yang

Front. Biosci. (Landmark Ed) 2017, 22(4), 558–569; https://doi.org/10.2741/4502
Published: 1 January 2017
(This article belongs to the Special Issue Homeostasis and therapeutical potential of CD4)
Abstract

Collagen deposition is a hallmark of atherosclerosis. Although compromised collagen I degradation has been implied in the pathogenesis of atherosclerosis, the molecular mechanisms are still unclear. Thus, we determined the role of CD38, an enzyme involved in cellular calcium modulation and autophagic flux, in the regulation of collagen I degradation in coronary arterial myocytes (CAMs). In primary cultured CAMs from CD38-/- mice, collagen I protein accumulation but not mRNA abundance was significantly increased compared with cells from CD38+/+ mice either under control or upon TGF-β stimulation. Pharmacological inhibition of the formation of autophagosomes with 3-methyladenine or of autophagolysosomes with a lysosomal functional blocker, bafilomycin A1, induced a similar increase in collagen protein levels, while inhibition of the proteasome by MG132 had no effects on collagen I accumulation. In addition, CD38-deficiency did not change the protein expression of matrix metalloprotein-9 (MMP-9) or tissue inhibitor of metalloproteinase-1 (TIMP-1) in CAMs. Confocal microscopy showed that collagen I deposition was mainly lied within lysosomes or autophagosomes in CD38-/- or TGF-β treated CAMs. Collagen I deposition increased when CAMs lack CD38 expression or if autophagy was blocked, which is associated with impaired autophagic degradation of collagen I. This CD38 regulation of autophagic flux may represent a novel mechanism for extracellular matrix (ECM) plasticity of coronary arteries upon atherogenic stimulation.

Keywords
CD38
Collagen
Autophagy
Coronary Artery
Mouse
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