Inhibition of microRNA‐103 attenuates inflammation and endoplasmic reticulum stress in atherosclerosis through disrupting the PTEN‐mediated MAPK signaling

Abstract

Atherosclerosis (AS), a chronic disorder of large arteries, is the underlying pathological process of heart disease and stroke. Former researchers have found that microRNAs (miRs) are involved in the several key processes of AS. Apolipoprotein E knockout (ApoE −/− ) mice fed a high-fat-diet (HFD) to establish AS model. The expression of miR-103 was characterized in the mice model. The effects of miR-103 on inflammation and endoplasmic reticulum stress (ERS) were analyzed when the expression of miR-103 was inhibited in ApoE −/− mice fed an HFD and human aortic endothelial cells (HAECs) exposed to oxidized low-density lipoprotein (ox-LDL). The relationship between miR-103 and phosphatase and tensin homolog (PTEN) was identified by luciferase activity detection and real-time quantitative polymerase chain reaction (RT-qPCR). Gain-and loss-function approaches were further applied for investigating the regulatory effects of miR-103 and PTEN on ERS. Role of MAPK signaling was then analyzed using PD98059 to block this pathway. miR-103 was highly expressed in the ApoEApoE −/− mice fed an HFD. Downregulation of miR-103 suppressed inflammation and ERS in endothelial cells isolated from ApoE −/− mice fed a HFD and ox-LDL-exposed HAECs. In addition, miR-103 can target PTEN and downregulate its expression. Overexpression of PTEN reversed the miR-103-induced activation of MAPK signaling. Moreover, PTEN upregulation or MAPK signaling inhibition ease miR-103-induced inflammation and ERS in vivo and in vitro. Thus, miR-103 depletion restrains the progression of AS through blocking PTEN-mediated MAPK signaling.

Identifying the pattern of immune related cells and genes in the peripheral blood of ischemic stroke

“…However, PTEN has been reported to be inhibited by many microRNA (miRNA) and performed neuroprotective effect against ischemic stroke in experimental models. miR-103 can target PTEN and downregulate its expression, which depletion restrains the progression of atherosclerosis through blocking PTEN-mediated MAPK signaling [ 11 ]. Another data demonstrates that miR-130a prevented cerebral ischemia/reperfusion damage against ischemic stroke by mediating the PTEN/PI3K/AKT pathway [ 12 ].…”

Involvement of Myeloid Cells and Noncoding RNA in Abdominal Aortic Aneurysm Disease

“…Contributions from miRNAs to inflammatory processes have been demonstrated for a multitude of diseases (123), including rheumatoid arthritis (126), psoriasis (124), asthma (78), ulcerative colitis (147), systemic lupus erythematosus (133), different forms of glomerulonephritis (93), and also atherosclerosis (51,127).…”

“…Color images are available online. model (51). Depletion of miR-103 was shown to counteract atherosclerosis through blocking phosphatase and tensin homolog (PTEN)-mediated mitogen-activated protein kinase (MAPK) signaling (51).…”

MicroRNA-103 Protects Coronary Artery Endothelial Cells against H2O2-Induced Oxidative Stress via BNIP3-Mediated End-Stage Autophagy and Antipyroptosis Pathways

“…Alternatively, reduced expression of miR-103 limits the occurrence of AS by preventing miR-103-induced lncwdr59 inhibition, thereby protecting endothelial cells from endothelial damage and reducing the targeted inhibition of Kruppel-like factor 4 (kfl4) [20]. Other studies have found that low miR-103 expression results in enhanced expression of the downstream target gene, phosphatase, and tensin homolog deleted on chromosome 10 (PTEN), which inhibits the p38 mitogen-activated protein kinase (MAPK) signaling pathway and reduces the inflammatory response and ER stress response in endothelial cells exposed to oxidized low-density lipoprotein (ox-LDL) [21]. Moreover, miR-103 knockout reduces the necrosis of H9C2 cells treated with H 2 O 2 , by regulating the downstream target gene Fas-associating protein with death domain (FADD) and preventing the formation of the ripk1/ripk3 complex [22].…”

“…In addition, low miR-103 expression reduces the formation of the ripk1/ripk3 complex by activating FADD and effectively reducing the occurrence of myocardial necrosis induced by oxidative stress [22]. Moreover, in hyperlipidemia, miR-103 promotes endothelial cell regeneration, reduces or suppresses PTEN/MAPK signaling by promoting the expression of lncwdr59, and attenuates cell damage caused by endoplasmic reticulum stress [20,21]. However, other studies suggest that low miR-103 expression may cause cell damage.…”