ALK5 deficiency inhibits macrophage inflammation and lipid loading by targeting KLF4. Issue 3 (4th March 2020)

• Record Type: Journal Article
• Authors: Li, Wenyan; Wang, Junhua; Li, Zhaofeng
• Is Part Of: Bioscience reports. Volume 40:Issue 3(2020)
• Publication Date: 2020-03-04
• Subjects: ALK5 -- foam cell -- inflammation -- KLF4 -- macrophage; Molecular biology -- Periodicals; Cytology -- Periodicals; 572.8
• DOI: 10.1042/BSR20194188
• Languages: English
• ISSNs: 0144-8463

Abstract

Abstract: The transforming growth factor type-β (TGF-β) has been demonstrated to play an important role in the development of atherosclerosis through binding to the serine/threonine kinase transmembrane type I and type II receptors. However, as a key type I receptor for TGF-β, the exact role and the underlying mechanism of Activin receptor-like kinase 5 (ALK5) on macrophage activation involved in atherogenesis remain unclear. In the present study, enhanced ALK5 expression was found in bone marrow derived macrophages (BMDMs) upon OX-LDL stimulation tested by RT-PCR and Western blot, which was further verified by co-immunofluorescence staining. Next, the loss-of-function of ALK5 used AdshALK5 transfection was performed to test the effect of ALK5 on macrophage activation. We observed that ALK5 silencing inhibited pro-inflammatory but promoted anti-inflammatory macrophage markers expression. Moreover, decreased foam cell formation was found in ALK5 knockdown macrophages accompanied by increased cholesterol efflux. Mechanistically, ALK5 knockdown significantly increased KLF4 expression that was responsible for the attenuated macrophage activation induced by ALK5 knockdown. Collectively, these findings suggested that neutralization of ALK5 may act as a promising strategy for the management of atherosclerosis.