Abnormal Lysosomal Positioning and Small Extracellular Vesicle Secretion in Arterial Stiffening and Calcification of Mice Lacking Mucolipin 1 Gene

International Journal of Molecular Sciences
Owais M BhatPin-Lan Li

Abstract

Recent studies have shown that arterial medial calcification is mediated by abnormal release of exosomes/small extracellular vesicles from vascular smooth muscle cells (VSMCs) and that small extracellular vesicle (sEV) secretion from cells is associated with lysosome activity. The present study was designed to investigate whether lysosomal expression of mucolipin-1, a product of the mouse Mcoln1 gene, contributes to lysosomal positioning and sEV secretion, thereby leading to arterial medial calcification (AMC) and stiffening. In Mcoln1-/- mice, we found that a high dose of vitamin D (Vit D; 500,000 IU/kg/day) resulted in increased AMC compared to their wild-type littermates, which was accompanied by significant downregulation of SM22-α and upregulation of RUNX2 and osteopontin in the arterial media, indicating a phenotypic switch to osteogenic. It was also shown that significantly decreased co-localization of lysosome marker (Lamp-1) with lysosome coupling marker (Rab 7 and ALG-2) in the aortic wall of Mcoln1-/- mice as compared to their wild-type littermates. Besides, Mcoln1-/- mice showed significant increase in the expression of exosome/ sEV markers, CD63, and annexin-II (AnX2) in the arterial medial wall, accompanied by sig...Continue Reading

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Citations

Apr 8, 2020·International Journal of Molecular Sciences·Yi-Chou HouKuo-Cheng Lu
Dec 2, 2020·International Journal of Molecular Sciences·Cédric H G NeutelPieter-Jan Guns
Nov 10, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Shuangshuang DuChunli Song

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Methods Mentioned

BETA
PCR
confocal microscopy
blood collection
light microscopy
light scattering

Software Mentioned

Image J
NTA
PRISM
Pro Plus
Image

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