MicroRNA-712 restrains macrophage pro-inflammatory responses by targeting LRRK2 leading to restoration of insulin stimulated glucose uptake by myoblasts

Talari, Malathi; Nayak, Tapan K.; Kain, Vasundhara; Babu, Phanithi Prakash; Misra, Parimal; Parsa, Kishore V. L.

doi:10.1016/j.molimm.2016.12.014

Cited by 10 publications

(5 citation statements)

References 31 publications

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“…revealed that exercise training restores the cardiac miR-1 and miR-214 levels to improve ventricular function in myocardial infarction in rats 35 . Additionally, miR-712 restrains pro-inflammatory responses in macrophages to restore insulin-stimulated glucose uptake by myoblasts 36 . Furthermore, our experimental results revealed that silencing MALAT1 ameliorated IR by elevating miR-382-3p and disrupting resistin, which was evidenced by the promoted glucose uptake, elevated levels of NO and p-Akt/Akt, inhibited cell migration, and decreased levels of Ang II, TNF-α, IL-6, sICAM-1, sVCAM-1, ET-1, and p-IRS/ISR-1 in IR cell model.…”

Section: Discussionmentioning

confidence: 99%

Exercise Reduces Insulin Resistance in Type 2 Diabetes Mellitus via Mediating the lncRNA MALAT1/MicroRNA-382-3p/Resistin Axis

Liu

Fan

Xie

et al. 2019

Molecular Therapy - Nucleic Acids

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Insulin resistance (IR) is the primary pathological mechanism underlying type 2 diabetes mellitus (T2DM). Here, the study aimed to ascertain whether and how exercise mediates IR in T2DM. An in vivo mouse model of high-fat diet-induced IR and an in vitro high-glucose-induced IR model were constructed. High long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression was detected in T2MD and was positively correlated with HOMA-IR and resistin levels. Then, short hairpin RNA targeting MALAT1 (sh-MALAT1) or pcDNA-MALAT1 was delivered into human umbilical vein endothelial cells (HUVECs) to knock down or upregulate its expression, respectively. Silencing of MALAT1 resulted in reduced levels of resistin, Ang II, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelin-1 (ET-1), and p-insulin receptor substrate-1 (p-IRS)/ISR-1, and decreased cell migration, as well as enhanced glucose uptake and levels of nitric oxide (NO) and p-Akt/Akt. In the IR mouse model, exercise was observed to downregulate MALAT1 to reduce resistin, whereby exercise reduced homeostatic model assessment-insulin resistance (HOMA-IR). Besides, exercise also elevated microRNA-382-3p (miR-382-3p) expression in the serum of IR mice. Dual-luciferase reporter and RNA binding protein immunoprecipitation (RIP) assays identified that MALAT1 could bind to miR-382-3p to upregulate resistin. Collectively, the key observations of the study provide evidence that inhibition of MALAT1 elevates miR-382-3p to repress resistin, which consequently underlies the mechanism of exercise protecting against IR, highlighting a direction for T2DM therapy development.

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Section: Discussionmentioning

confidence: 99%

Exercise Reduces Insulin Resistance in Type 2 Diabetes Mellitus via Mediating the lncRNA MALAT1/MicroRNA-382-3p/Resistin Axis

Liu

Fan

Xie

et al. 2019

Molecular Therapy - Nucleic Acids

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“…Many studies have implicated that miRNAs confer important effects on macrophage polarization in kinds of diseases [25][26][27]. Accumulating studies have well documented that some miRNAs are capable of regulating inflammation and insulin resistance in diabetes by influencing macrophage polarization [28][29][30]. Nonetheless, little is known of the altering effects of miRNAs on GDM development and progression by regulating macrophage differentiation and functions.…”

Section: Mediators Of Inflammationmentioning

confidence: 99%

miR-657 Promotes Macrophage Polarization toward M1 by Targeting FAM46C in Gestational Diabetes Mellitus

Wang

Liu

et al. 2019

Mediators of Inflammation

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MicroRNA (miRNA) has been widely suggested to play a vital role of in the pathogenesis of gestational diabetes mellitus (GDM). We have previously demonstrated that miR-657 can regulate macrophage inflammatory response in GDM. However, the role of miR-657 on M1/M2 macrophage polarization in GDM pathogenesis is not clear yet. This study is aimed at elucidating this issue and identifying novel potential GDM therapeutic targets based on miRNA network. miR-657 is found to be upregulated in placental macrophages demonstrated by real-time PCR, which can enhance macrophage proliferation and migration in vitro. Luciferase reporter assay shows the evidence that FAM46C is a target of miR-657. In addition, miR-657 can promote macrophage polarization toward the M1 phenotype by downregulating FAM46C in macrophages. The present study strongly suggests miR-657 is involved in GDM pathogenesis by regulating macrophage proliferation, migration, and polarization via targeting FAM46C. miR-657/FAM46C may serve as promising targets for GDM diagnosis and treatment.

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“…e 3′UTR of the Lrrk2 gene would have been a target of miR-712 and then dampens the phosphorylation of p38 and ERK1/2 kinases. However, miR-712 restored insulin-stimulated glucose uptake by myoblasts through downregulating macrophage-mediated inflammatory response [32]. A study in 123 patients and 46 agematched controls reported the addition of reactive oxygen species, obesity, low adiponectin, and high glucose and interleukin-6 as cause of the abatement in Irak3 in THP-1 cells in vitro [33].…”

Section: Discussionmentioning

confidence: 99%

RNA‐Seq Analysis of the Liver Transcriptome Reveals the Networks Regulating Treatment of Sitagliptin Phosphate plus Fuzhujiangtang Granule in the Zucker Diabetic Fatty Rats

Guo

Sun

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Diabetes is one of the most serious chronic diseases. Numerous drugs including oral agents and traditional Chinese medicines, such as sitagliptin phosphate (SP) and Fuzhujiangtang granules (FJG), have been discovered to treat diabetes and used in combination in clinical practice. However, the exact effect and underlying mechanism of using combined medicine is not clear. In this study, we compared the antidiabetic effect of SP, FJG, and SP plus FJG (SP-FJG) using forty 8-week-old Zucker diabetic fatty (ZDF) rats and 10 age-matched Zucker lean rats as the normal control group. ZDF rats were treated with different therapies, respectively, for 6 weeks. The study showed that the fast blood glucose, random blood glucose (RBG), oral glucose tolerance test (OGTT), insulin tolerance test (ITT), homeostasis model of assessment-insulin resistance index, triglyceride (TC), superoxide dismutase, and malondialdehyde of each treatment group were improved when compared with the diabetes mellitus (DM) control group. Using SP-FJG in combination had better improvements in OGTT, fast serum insulin levels, TNF-α, and IL-6 compared with using SP individually. Besides, the increased LDL and TC caused by using SP was attenuated by using FJG in combination. Meanwhile, compared with the DM group, 1781 differentially expressed genes (DEGs) (including 1248 mRNA, 211 ncRNA, 202 cirRNA, and 120 miRNA) were enriched in 58 pathways. Through analysis of ceRNA networks, we found that rno-miR-326-3p, rno-miR-423-5p, rno-miR-15b-5p, rno-let-7c-5p, and rno-let-7b-5p were related to pharmacodynamics in different groups. By analyzing the protein-protein interaction (PPI) and coexpression networks of the transcriptomes of different groups, it is inferred that Lrrk2 and Irak3 may be pharmacodynamic genes for type 2 diabetes mellitus (T2DM). Our research compared the treatment of SP, FJG, and SP-FJG and acquainted the PPI network, coexpression network, mutations, and pharmacodynamics genes, which reveals the new mechanisms of pathogenesis of T2DM.

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MicroRNA-712 restrains macrophage pro-inflammatory responses by targeting LRRK2 leading to restoration of insulin stimulated glucose uptake by myoblasts

Cited by 10 publications

References 31 publications

Exercise Reduces Insulin Resistance in Type 2 Diabetes Mellitus via Mediating the lncRNA MALAT1/MicroRNA-382-3p/Resistin Axis

Exercise Reduces Insulin Resistance in Type 2 Diabetes Mellitus via Mediating the lncRNA MALAT1/MicroRNA-382-3p/Resistin Axis

miR-657 Promotes Macrophage Polarization toward M1 by Targeting FAM46C in Gestational Diabetes Mellitus

RNA‐Seq Analysis of the Liver Transcriptome Reveals the Networks Regulating Treatment of Sitagliptin Phosphate plus Fuzhujiangtang Granule in the Zucker Diabetic Fatty Rats

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