MicroRNA-99a mimics inhibit M1 macrophage phenotype and adipose tissue inflammation by targeting TNFα.

Cellular & Molecular Immunology
Anant JaiswalManoj Kumar Barthwal

Abstract

In human adipose tissue and obesity, miR-99a expression is negatively correlated with inflammation. Therefore, the present study investigated the role of miR-99a in macrophage phenotype activation and adipose tissue inflammation. M2 BMDMs showed a significant increase in miR-99a expression when compared to the M0 and M1 phenotypes. Phenotype-switching experiments established an association between upregulated miR-99a expression and the M2 phenotype. Overexpression of miR-99a prevented M1 phenotype activation and attenuated bactericidal activity. Likewise, knockdown of miR-99a abolished M2 phenotype activation. By means of in silico target prediction tools and a luciferase reporter assay, TNFα was identified as a direct target of miR-99a. Knockdown of TNFα recapitulated the effect of miR-99a overexpression in M1 BMDMs. In a db/db mice model, miR-99a expression was reduced in eWAT and F4/80+ ATMs. Systemic overexpression of miR-99a in db/db mice attenuated adipocyte hypertrophy with increased CD301 and reduced CD86 immunostaining. Flow cytometry analysis also showed an increased M2 and a reduced M1 macrophage population. Mimics of miR-99a also improved the diabetic dyslipidemia and insulin signaling in eWAT and liver, with an att...Continue Reading

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Citations

Mar 30, 2020·Proceedings of the National Academy of Sciences of the United States of America·Devaraj BasavarajappaOlof Rådmark
Oct 31, 2019·Cellular & Molecular Immunology·Siyuan ChenXiawei Wei
Jul 1, 2020·Cells·Anastasiya S PoltavetsTimur Kh Fatkhudinov
Sep 15, 2020·Frontiers in Immunology·Morgan C Nelson, Ryan M O'Connell
Nov 25, 2020·Wiley Interdisciplinary Reviews. RNA·Joseph Eniafe, Shuai Jiang
Nov 27, 2020·Frontiers in Cardiovascular Medicine·Alexander E BerezinMichael Lichtenauer
Dec 31, 2020·Journal of Personalized Medicine·Gennaro MartucciVitale Miceli
Feb 24, 2021·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Yu ZhangLingmin Zhou
Mar 20, 2021·Free Radical Biology & Medicine·Sukka Santosh ReddyManoj Kumar Barthwal
May 22, 2021·Frontiers in Pharmacology·Xiaoxiao ZhuXia Li
May 20, 2021·Mediators of Inflammation·Pingping WangZengfang Wang
Jun 12, 2021·International Journal of Oral Science·Yiming ChenXuliang Deng
Jul 1, 2021·Cell & Bioscience·Mei ZhangXin-Hua Liang
Aug 13, 2021·Cellular & Molecular Immunology·Mohita Maurya, Manoj Kumar Barthwal
Jan 19, 2021·ACS Biomaterials Science & Engineering·Xiuhong HuangChangren Zhou

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Methods Mentioned

BETA
FACS
PCR
transfection
ELISA
flow cytometry

Software Mentioned

TargetScan
FACS Diva
miRanda
DIANA
Image Quant
ImageJ Image Processing and Analysis
RNA22
miRDB
RNAhybrid
miRwalk

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