Blockade of lncRNA-ASLNCS5088-enriched exosome generation in M2 macrophages by GW4869 dampens the effect of M2 macrophages on orchestrating fibroblast activation

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Jialin ChenChen Wang

Abstract

In hypertrophic scar (HS) formation, the type 2 immune response induces the alternatively activated macrophages (M2), which manipulate fibroblasts to differentiate into myofibroblasts with active biologic functions and proliferation. Myofibroblasts express α-smooth muscle actin (α-SMA) and synthesize and produce additional collagen type I and collagen type III, inducing HS formation. However, studies on the mechanism of M2 macrophage modulation are only based on the recognition of profibrotic factors such as TGF-β1 secreted by macrophages. The influence of exosomes from M2 macrophages on scar formation is still unknown. Both M2 macrophages and myofibroblasts highly express glutaminases (GLSs). GLS is a critical enzyme in glutaminolysis and is important for M2 macrophage and fibroblast polarization. In this study, we found that in a TGF-β1-stimulated coculture system, a long noncoding RNA (lncRNA) named lncRNA-ASLNCS5088 was enriched in M2 macrophage-derived exosomes. This lncRNA could be transferred with high efficiency to fibroblasts and acted as an endogenous sponge to adsorb microRNA-200c-3p, resulting in increased GLS and α-SMA expression. Pretreatment with GW4869, which impairs M2 macrophage exosome synthesis, ameliorated ...Continue Reading

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Citations

Mar 31, 2020·Journal of Hematology & Oncology·Ming YiKongming Wu
Aug 14, 2020·International Reviews of Immunology·Yuyang HouDong Li
May 28, 2020·Trends in Cancer·Wei Yan, Shuai Jiang
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Apr 2, 2021·Molecular and Cellular Biochemistry·Xian-Min LiTian-Lan Zhao
Aug 31, 2021·The Journal of Investigative Dermatology·Anesh PrasaiAmina El Ayadi
Sep 19, 2021·Journal of Cosmetic Dermatology·Xu ShenLi Zeng

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