Exp Clin Endocrinol Diabetes 2021; 129(02): 131-137
DOI: 10.1055/a-1012-8420
Article

Downregulation of miR-320 Alleviates Endoplasmic Reticulum Stress and Inflammatory Response in 3T3-L1 Adipocytes

Lu Liu
1   Department of Endocrinology, Seventh Peopleʼs Hospital of Shanghai University of TCM, Shanghai, China
,
Xiaohua Li
1   Department of Endocrinology, Seventh Peopleʼs Hospital of Shanghai University of TCM, Shanghai, China
› Author Affiliations

Abstract

Objective MicroRNAs serve important roles in the regulation of endoplasmic reticulum stress (ERs). This study aimed to investigate the role of microRNA-320 (miR-320) in the development of ERs and the inflammatory response in 3T3-L1 adipocytes.

Materials and Methods The adipose tissue expression levels of miR-320 and ERs markers (GRP78, GRP94, Derlin-1 and CHOP) and the serum concentration of inflammatory cytokines (TNF-α, NF-κB and IL-6) in obese patients were evaluated using quantitative real-time RT-PCR or enzyme-linked immunosorbent assay. The correlation of miR-320 with genes involved in ERs and inflammation was analyzed. The effects of miR-320 on ERs and inflammation were explored using mature 3T3-L1 adipocytes, which were pretreated with palmitic acid (PA).

Results ERs markers and inflammatory cytokines were all upregulated in obese patients. Adipose tissue miR-320 expression was also increased in obese patients, and had positive correlations with the levels of ERs markers and inflammatory cytokines. After PA treatment, the levels of ERs markers and inflammatory cytokines were elevated significantly in 3T3-L1 adipocytes. Moreover, miR-320 expression was increased in the cells under ERs status. The upregulation of miR-320 could enhance the expression of ERs markers and inflammatory cytokines, but the downregulation of miR-320 resulted in the opposite results.

Conclusion The data of this study indicate that miR-320 expression is upregulated in ERs status, and the downregulation of miR-320 ameliorates ERs and the inflammatory response in 3T3-L1 adipocytes. We consider that the approaches to decrease miR-320 expression may be novel therapeutic strategies for the treatment of obesity and obesity-related diseases.



Publication History

Received: 03 June 2019
Received: 09 September 2019

Accepted: 12 September 2019

Article published online:
21 October 2019

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Tamura Y. Ectopic fat, insulin resistance and metabolic disease in non-obese Asians: Investigating metabolic gradation. Endocr J 2019; 66: 1-9
  • 2 Li Y, Li S, Zhai Q. et al. Association of GSTs polymorphisms with risk of gestational diabetes mellitus. Int J Clin Exp Pathol 2015; 8: 15191-15197
  • 3 Vargo PR, Steffen RJ, Bakaeen FG. et al. The impact of obesity on cardiac surgery outcomes. J Card Surg 2018; 33: 588-594
  • 4 Majdoubi A, Kishta OA, Thibodeau J. Role of antigen presentation in the production of pro-inflammatory cytokines in obese adipose tissue. Cytokine 2016; 82: 112-121
  • 5 Cnop M, Foufelle F, Velloso LA. Endoplasmic reticulum stress, obesity and diabetes. Trends Mol Med 2012; 18: 59-68
  • 6 Hotamisligil GS. Inflammation and endoplasmic reticulum stress in obesity and diabetes. Int J Obes (Lond) 2008; 32 Suppl 7 S52-54
  • 7 Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 2010; 140: 900-917
  • 8 Hummasti S, Hotamisligil GS. Endoplasmic reticulum stress and inflammation in obesity and diabetes. Circ Res 2010; 107: 579-591
  • 9 Xu H, Barnes GT, Yang Q. et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003; 112: 1821-1830
  • 10 Hirata T, Kawai T, Hirose H. et al. Palmitic acid-rich diet suppresses glucose-stimulated insulin secretion (GSIS) and induces endoplasmic reticulum (ER) stress in pancreatic islets in mice. Endocr Res 2016; 41: 8-15
  • 11 Li Y, Yang J, Chen MH. et al. Ilexgenin A inhibits endoplasmic reticulum stress and ameliorates endothelial dysfunction via suppression of TXNIP/NLRP3 inflammasome activation in an AMPK dependent manner. Pharmacol Res 2015; 99: 101-115
  • 12 Zeeshan HM, Lee GH, Kim HR. et al. Endoplasmic Reticulum Stress and Associated ROS. Int J Mol Sci 2016; 17: 327
  • 13 Kim OK, Jun W, Lee J. Mechanism of ER Stress and Inflammation for Hepatic Insulin Resistance in Obesity. Ann Nutr Metab 2015; 67: 218-227
  • 14 Sasaki K, Yoshida H. Organelle autoregulation-stress responses in the ER, Golgi, mitochondria and lysosome. J Biochem 2015; 157: 185-195
  • 15 Xu L, Wang ZH, Xu D. et al. Expression of Derlin-1 and its effect on expression of autophagy marker genes under endoplasmic reticulum stress in lung cancer cells. Cancer Cell Int 2014; 14: 50
  • 16 Zhu G, Lee AS. Role of the unfolded protein response, GRP78 and GRP94 in organ homeostasis. J Cell Physiol 2015; 230: 1413-1420
  • 17 Greene MW, Ruhoff MS, Burrington CM. et al. TNFalpha activation of PKCdelta, mediated by NFkappaB and ER stress, cross-talks with the insulin signaling cascade. Cell Signal 2010; 22: 274-284
  • 18 Deng J, Lu PD, Zhang Y. et al. Translational repression mediates activation of nuclear factor kappa B by phosphorylated translation initiation factor 2. Mol Cell Biol 2004; 24: 10161-10168
  • 19 Zhang K, Kaufman RJ. From endoplasmic-reticulum stress to the inflammatory response. Nature 2008; 454: 455-462
  • 20 Ameres SL, Zamore PD. Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol 2013; 14: 475-488
  • 21 Bartel DP.. MicroRNAs: target recognition and regulatory functions. Cell 2009; 136: 215-233
  • 22 Jia B, Zhang Z, Qiu X. et al. Analysis of the miRNA and mRNA involved in osteogenesis of adipose-derived mesenchymal stem cells. Exp Ther Med 2018; 16: 1111-1120
  • 23 Chitnis NS, Pytel D, Bobrovnikova-Marjon E. et al. miR-211 is a prosurvival microRNA that regulates chop expression in a PERK-dependent manner. Mol Cell 2012; 48: 353-364
  • 24 Dai BH, Geng L, Wang Y. et al. microRNA-199a-5p protects hepatocytes from bile acid-induced sustained endoplasmic reticulum stress. Cell Death Dis 2013; 4: e604
  • 25 Zhang X, Yuan Y, Jiang L. et al. Endoplasmic reticulum stress induced by tunicamycin and thapsigargin protects against transient ischemic brain injury: Involvement of PARK2-dependent mitophagy. Autophagy 2014; 10: 1801-1813
  • 26 Wang S, Huang Y, Zhou C. et al. The role of autophagy and related MicroRNAs in inflammatory bowel disease. Gastroenterol Res Pract 2018; 2018: 7565076
  • 27 Meng F, Zhang Z, Chen W. et al. MicroRNA-320 regulates matrix metalloproteinase-13 expression in chondrogenesis and interleukin-1beta-induced chondrocyte responses. Osteoarthritis Cartilage 2016; 24: 932-941
  • 28 Lopetuso LR, De Salvo C, Pastorelli L. et al. IL-33 promotes recovery from acute colitis by inducing miR-320 to stimulate epithelial restitution and repair. Proc Natl Acad Sci USA 2018; 115: E9362-E9370
  • 29 Feng B, Chakrabarti S. miR-320 Regulates Glucose-Induced Gene Expression in Diabetes. ISRN Endocrinol 2012; 2012: 549875
  • 30 Ling HY, Ou HS, Feng SD. et al. CHANGES IN microRNA (miR) profile and effects of miR-320 in insulin-resistant 3T3-L1 adipocytes. Clin Exp Pharmacol Physiol 2009; 36: e32-39
  • 31 Jia Y, Weng Z, Wang C. et al. Increased chemosensitivity and radiosensitivity of human breast cancer cell lines treated with novel functionalized single-walled carbon nanotubes. Oncol Lett 2017; 13: 206-214
  • 32 Cui X, You L, Zhu L. et al. Change in circulating microRNA profile of obese children indicates future risk of adult diabetes. Metabolism 2018; 78: 95-105
  • 33 Heinrich M, Daniels R, Stintzing FC. et al. Comprehensive phytochemical characterization of St. Johnʼs wort (Hypericum perforatum L.) oil macerates obtained by different extraction protocols via analytical tools applicable in routine control. Pharmazie 2017; 72: 131-138
  • 34 Ying W, Riopel M, Bandyopadhyay G. et al. Adipose Tissue Macrophage-Derived Exosomal miRNAs Can Modulate In Vivo and In Vitro Insulin Sensitivity. Cell 2017; 171: 372-384 e312
  • 35 Dumortier O, Hinault C, Van Obberghen E. MicroRNAs and metabolism crosstalk in energy homeostasis. Cell Metab 2013; 18: 312-324
  • 36 Mennigen JA. Micromanaging metabolism-a role for miRNAs in teleost energy metabolism. Comp Biochem Physiol B Biochem Mol Biol 2016; 199: 115-125
  • 37 Diniz GP, Huang ZP, Liu J. et al. Loss of microRNA-22 prevents high-fat diet induced dyslipidemia and increases energy expenditure without affecting cardiac hypertrophy. Clin Sci (Lond) 2017; 131: 2885-2900
  • 38 Teleman AA, Maitra S, Cohen SM. Drosophila lacking microRNA miR-278 are defective in energy homeostasis. Genes Dev 2006; 20: 417-422
  • 39 Xu P, Vernooy SY, Guo M. et al. The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism. Curr Biol 2003; 13: 790-795
  • 40 Poy MN, Spranger M, Stoffel M. microRNAs and the regulation of glucose and lipid metabolism. Diabetes Obes Metab 2007; 9 Suppl 2 67-73
  • 41 Ghorbani S, Mahdavi R, Alipoor B. et al. Decreased serum microRNA-21 level is associated with obesity in healthy and type 2 diabetic subjects. Arch Physiol Biochem 2017; 1-6
  • 42 Chen M, Ma G, Yue Y. et al. Downregulation of the miR-30 family microRNAs contributes to endoplasmic reticulum stress in cardiac muscle and vascular smooth muscle cells. Int J Cardiol 2014; 173: 65-73
  • 43 Yang Y, Hou N, Wang X. et al. miR-15b-5p induces endoplasmic reticulum stress and apoptosis in human hepatocellular carcinoma, both in vitro and in vivo, by suppressing Rab1A. Oncotarget 2015; 6: 16227-16238
  • 44 Li M, Zhang S, Qiu Y. et al. Upregulation of miR-665 promotes apoptosis and colitis in inflammatory bowel disease by repressing the endoplasmic reticulum stress components XBP1 and ORMDL3. Cell Death Dis 2017; 8: e2699
  • 45 Li G, Luna C, Qiu J. et al. Role of miR-204 in the regulation of apoptosis, endoplasmic reticulum stress response, and inflammation in human trabecular meshwork cells. Invest Ophthalmol Vis Sci 2011; 52: 2999-3007
  • 46 Zhang Z, Wu S, Muhammad S. et al. miR-103/107 promote ER stress-mediated apoptosis via targeting the Wnt3a/beta-catenin/ATF6 pathway in preadipocytes. J Lipid Res 2018; 59: 843-853
  • 47 Cui W, Wang S, Wang Z. et al. Inhibition of PTEN Attenuates Endoplasmic Reticulum Stress and Apoptosis via Activation of PI3K/AKT Pathway in Alzheimerʼs Disease. Neurochem Res 2017; 42: 3052-3060
  • 48 Pierdomenico M, Cesi V, Cucchiara S. et al. NOD2 Is Regulated By Mir-320 in Physiological Conditions but this Control Is Altered in Inflamed Tissues of Patients with Inflammatory Bowel Disease. Inflamm Bowel Dis 2016; 22: 315-326
  • 49 Byndloss MX, Keestra-Gounder AM, Baumler AJ. et al. NOD1 and NOD2: New Functions Linking Endoplasmic Reticulum Stress and Inflammation. DNA Cell Biol 2016; 35: 311-313