miR‑875‑5p regulates IR and inflammation via targeting TXNRD1 in gestational diabetes rats

Fu,Songbo; Fu,Songquan; Ma,Xiaoni; Yang,Xiaomei; Ling,Jizu

doi:10.3892/mmr.2021.11942

miR‑875‑5p regulates IR and inflammation via targeting TXNRD1 in gestational diabetes rats

Authors:
- Songbo Fu
- Songquan Fu
- Xiaoni Ma
- Xiaomei Yang
- Jizu Ling
View Affiliations

Affiliations: Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Department of Respiration, The First Hospital of Lanzhou City, Lanzhou, Gansu 730050, P.R. China, Department of Pediatrics, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
Published online on: February 25, 2021 https://doi.org/10.3892/mmr.2021.11942
Article Number: 303
Copyright: © Fu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Gestational diabetes mellitus (GDM) is a serious life‑threatening disease that affects the mother and fetus. However, the pathogenesis of GDM is still unclear. microRNAs (miRs) play vital roles in the regulation of various cell functions. The present study aimed to investigate the effects of miR‑875‑5p and thioredoxin reductase 1 cytoplasmic (TXNRD1) in GDM rats and analyze the associated underlying mechanism. A GDM rat model was induced using an intraperitoneal injection of streptozotocin. miR‑875‑5p knockdown plasmids or TXNRD1 knockdown plasmids were injected into the rats via the caudal vein. miR‑875‑5p and TXNRD1 expression in the serum were detected using reverse transcription‑quantitative PCR (RT‑qPCR) or western blot (WB) analyses. The fasting blood‑glucose (FBG), fasting serum insulin, triglyceride and high density lipoprotein levels were detected by specific commercial kits. The inflammatory response and the induction of oxidative stress were analyzed by assessing the expression of associated markers via WB, RT‑qPCR or commercial kits. The pancreatic and placental injuries were detected by hematoxylin and eosin staining. The results indicated that miR‑875‑5p expression levels were downregulated, whereas TXNRD1 levels were upregulated in GDM rats compared with normal pregnancy rats. miR‑875‑5p significantly regulated TXNRD1 expression in GDM rats. miR‑875‑5p silencing notably reduced FBG and insulin resistance, which was accompanied by reduced expression levels of blood lipid and pro‑inflammatory markers as well as reduced oxidative stress. However, the effects of miR‑875‑5p could be reversed by TXNRD1 silencing. Therefore, the present study indicated that miR‑875‑5p regulated IR and inflammation by targeting TXNRD1 in GDM rats. miR‑875‑5p and TXNRD1 may be considered as potential targets for treating GDM.

View Figures

View References

1	Metzger BE and Coustan DR; The Organizing Committee, : Summary and recommendations of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes Care. 21 (Suppl 2):B161–B167. 1998.PubMed/NCBI
2	Johns EC, Denison FC, Norman JE and Reynolds RM: Gestational Diabetes Mellitus: Mechanisms, Treatment, and Complications. Trends Endocrinol Metab. 29:743–754. 2018. View Article : Google Scholar : PubMed/NCBI
3	Hajifaraji M, Jahanjou F, Abbasalizadeh F, Aghamohammadzadeh N, Abbasi MM and Dolatkhah N: Effect of probiotic supplements in women with gestational diabetes mellitus on inflammation and oxidative stress biomarkers: A randomized clinical trial. Asia Pac J Clin Nutr. 27:581–591. 2018.PubMed/NCBI
4	Sha H, Zeng H, Zhao J and Jin H: Mangiferin ameliorates gestational diabetes mellitus-induced placental oxidative stress, inflammation and endoplasmic reticulum stress and improves fetal outcomes in mice. Eur J Pharmacol. 859:1725222019. View Article : Google Scholar : PubMed/NCBI
5	Baig S, Rizi EP, Shabeer M and Agrawal M: Heredity of type 2 diabetes confers increased susceptibility to oxidative stress and inflammation. BMJ Open Diabetes Res Care. 8:e0009452020. View Article : Google Scholar : PubMed/NCBI
6	Nazem MR, Asadi M, Jabbari N and Allameh A: Effects of zinc supplementation on superoxide dismutase activity and gene expression, and metabolic parameters in overweight type 2 diabetes patients: A randomized, double-blind, controlled trial. Clin Biochem. 69:15–20. 2019. View Article : Google Scholar : PubMed/NCBI
7	Sudharshana Murthy KA, Bhandiwada A, Chandan SL, Gowda SL and Sindhusree G: Evaluation of Oxidative Stress and Proinflammatory Cytokines in Gestational Diabetes Mellitus and Their Correlation with Pregnancy Outcome. Indian J Endocrinol Metab. 22:79–84. 2018. View Article : Google Scholar : PubMed/NCBI
8	Elliott HR, Sharp GC, Relton CL and Lawlor DA: Epigenetics and gestational diabetes: a review of epigenetic epidemiology studies and their use to explore epigenetic mediation and improve prediction. Diabetologia. 62:2171–2178. 2019. View Article : Google Scholar : PubMed/NCBI
9	Vasu S, Kumano K, Darden CM, Rahman I, Lawrence MC and Naziruddin B: MicroRNA Signatures as Future Biomarkers for Diagnosis of Diabetes States. Cells. 8:E15332019. View Article : Google Scholar : PubMed/NCBI
10	Zhao H and Tao S: miRNA-221 protects islet beta cell function in gestational diabetes mellitus by targeting PAK1. Biochem Biophys Res Commun. 520:218–224. 2008. View Article : Google Scholar
11	Zamanian Azodi M, Rezaei-Tavirani M, Rezaei-Tavirani M and Robati RM: Gestational Diabetes Mellitus Regulatory Network Identifies hsa-miR-145-5p and hsa-miR-875-5p as Potential Biomarkers. Int J Endocrinol Metab. 17:e866402019. View Article : Google Scholar : PubMed/NCBI
12	Xu Q, Zhu Q, Zhou Z, Wang Y, Liu X, Yin G, Tong X and Tu K: MicroRNA-876-5p inhibits epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma by targeting BCL6 corepressor like 1. Biomed Pharmacother. 103:645–652. 2018. View Article : Google Scholar : PubMed/NCBI
13	Zhang T, Cai X, Li Q, Xue P, Chen Z, Dong X and Xue Y: Hsa-miR-875-5p exerts tumor suppressor function through down-regulation of EGFR in colorectal carcinoma (CRC). Oncotarget. 7:42225–42240. 2016. View Article : Google Scholar : PubMed/NCBI
14	Cebula M, Schmidt EE and Arnér ES: TrxR1 as a potent regulator of the Nrf2-Keap1 response system. Antioxid Redox Signal. 23:823–853. 2015. View Article : Google Scholar : PubMed/NCBI
15	Kabuyama Y, Kitamura T, Yamaki J, Homma MK, Kikuchi SI and Homma Y: Involvement of thioredoxin reductase 1 in the regulation of redox balance and viability of rheumatoid synovial cells. Biochem Biophys Res Commun. 367:491–496. 2008. View Article : Google Scholar : PubMed/NCBI
16	Chang E, Kim DH, Yang H, Lee DH, Bae SH and Park CY: CB1 receptor blockade ameliorates hepatic fat infiltration and inflammation and increases Nrf2-AMPK pathway in a rat model of severely uncontrolled diabetes. PLoS One. 13:e02061522018. View Article : Google Scholar : PubMed/NCBI
17	Park HR, Lee SE, Yang H, Son GW, Jin YH and Park YS: Induction of Thioredoxin Reductase 1 by Korean Red Ginseng Water Extract Regulates Cytoprotective Effects on Human Endothelial Cells. Evid Based Complement Alternat Med. 2015:9720402015. View Article : Google Scholar : PubMed/NCBI
18	Raninga PV, Di Trapani G, Vuckovic S and Tonissen KF: TrxR1 inhibition overcomes both hypoxia-induced and acquired bortezomib resistance in multiple myeloma through NF-кβ inhibition. Cell Cycle. 15:559–572. 2016. View Article : Google Scholar : PubMed/NCBI
19	Matsui M, Oshima M, Oshima H, Takaku K, Maruyama T, Yodoi J and Taketo MM: Early embryonic lethality caused by targeted disruption of the mouse thioredoxin gene. Dev Biol. 178:179–185. 1996. View Article : Google Scholar : PubMed/NCBI
20	Shi X, Wang W, Zheng S, Zhang Q and Xu S: Selenomethionine relieves inflammation in the chicken trachea caused by LPS though inhibiting the NF-κB pathway. Biol Trace Elem Res. 194:525–535. 2020. View Article : Google Scholar : PubMed/NCBI
21	Ingram S, Mengozzi M, Heikal L, Mullen L and Ghezzi P: Inflammation-induced reactive nitrogen species cause proteasomal degradation of dimeric peroxiredoxin-1 in a mouse macrophage cell line. Free Radic Res. 53:875–881. 2019. View Article : Google Scholar : PubMed/NCBI
22	John CM, Ramasamy R, Al Naqeeb G, Al-Nuaimi AH and Adam A: Nicotinamide supplementation protects gestational diabetic rats by reducing oxidative stress and enhancing immune responses. Curr Med Chem. 19:5181–5186. 2012. View Article : Google Scholar : PubMed/NCBI
23	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
24	Bateman RM, Sharpe MD, Jagger JE, Ellis CG, Solé-Violán J, López-Rodríguez M, Herrera-Ramos E, Ruíz-Hernández J, Borderías L, Horcajada J, et al: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15–18 March 2016. Crit Care. 20:942016. View Article : Google Scholar : PubMed/NCBI
25	Kaushik SV, Plaisance EP, Kim T, Huang EY, Mahurin AJ, Grandjean PW and Mathews ST: Extended-release niacin decreases serum fetuin-A concentrations in individuals with metabolic syndrome. Diabetes Metab Res Rev. 25:427–434. 2009. View Article : Google Scholar : PubMed/NCBI
26	Skórzyńska-Dziduszko KE, Kimber-Trojnar Ż, Patro-Małysza J, Olszewska A, Zaborowski T and Małecka-Massalska T: An Interplay between Obesity and Inflammation in Gestational Diabetes Mellitus. Curr Pharm Biotechnol. 17:603–613. 2016. View Article : Google Scholar : PubMed/NCBI
27	Roca-Rodríguez MDM, López-Tinoco C, Fernández-Deudero Á, Murri M, García-Palacios MV, García-Valero MDA, Tinahones FJ and Aguilar-Diosdado M: Unfavorable cytokine and adhesion molecule profiles during and after pregnancy, in women with gestational diabetes mellitus. Endocrinol Diabetes Nutr. 64:18–25. 2017. View Article : Google Scholar : PubMed/NCBI
28	Poston L, Caleyachetty R, Cnattingius S, Corvalán C, Uauy R, Herring S and Gillman MW: Preconceptional and maternal obesity: epidemiology and health consequences. Lancet Diabetes Endocrinol. 12:1025–1036. 2016. View Article : Google Scholar
29	Tinkov AA, Bjørklund G, Skalny AV, Holmgren A, Skalnaya MG, Chirumbolo S and Aaseth J: The role of the thioredoxin/thioredoxin reductase system in the metabolic syndrome: Towards a possible prognostic marker? Cell Mol Life Sci. 75:1567–1586. 2018. View Article : Google Scholar : PubMed/NCBI
30	Feng Y, Feng Q, Qu H, Song X, Hu J, Xu X, Zhang L and Yin S: Stress adaptation is associated with insulin resistance in women with gestational diabetes mellitus. Nutr Diab. 10:42020. View Article : Google Scholar
31	Rueangdetnarong H, Sekararithi R, Jaiwongkam T, Kumfu S, Chattipakorn N, Tongsong T and Jatavan P: Comparisons of the oxidative stress biomarkers levels in gestational diabetes mellitus (GDM) and non-GDM among Thai population: cohort study. Endocrine Connect. 7:681–687. 2018. View Article : Google Scholar
32	Zygula A, Kosinski P, Zwierzchowska A, Sochacka M, Wroczynski P, Makarewicz-Wujec M, Pietrzak B, Wielgos M, Rzentala M and Giebultowicz J: Oxidative stress markers in saliva and plasma differ between diet-controlled and insulin-controlled gestational diabetes mellitus. Diabetes Res Clin Pract. 148:72–80. 2019. View Article : Google Scholar : PubMed/NCBI
33	Ren X, Zou L, Lu J and Holmgren A: Selenocysteine in mammalian thioredoxin reductase and application of ebselen as a therapeutic. Free Radic Biol Med. 127:238–247. 2018. View Article : Google Scholar : PubMed/NCBI
34	Lu J and Holmgren A: The thioredoxin antioxidant system. Free Radic Biol Med. 66:75–87. 2014. View Article : Google Scholar : PubMed/NCBI
35	Arnér ESJ: Focus on mammalian thioredoxin reductases - Important selenoproteins with versatile functions. Biochim Biophys Acta. 1790:495–526. 2009. View Article : Google Scholar : PubMed/NCBI
36	Bobba A, Casalino E, Petragallo VA and Atlante A: Thioredoxin/thioredoxin reductase system involvement in cerebellar granule cell apoptosis. Apoptosis. 19:1497–1508. 2014. View Article : Google Scholar : PubMed/NCBI
37	Sun QA, Wu Y, Zappacosta F, Jeang KT, Lee BJ, Hatfield DL and Gladyshev VN: Redox Regulation of Cell Signaling by Selenocysteine in Mammalian Thioredoxin Reductases. J Biol Chem. 274:24522–24530. 1999. View Article : Google Scholar : PubMed/NCBI
38	He L, He T, Farrar S, Ji L, Liu T and Ma X: Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species. Cell Physiol Biochem. 44:532–553. 2017. View Article : Google Scholar : PubMed/NCBI
39	Calabrese V, Mancuso C, Sapienza M, Puleo E, Calafato S, Cornelius C, Finocchiaro M, Mangiameli A, Di Mauro M, Stella AM and Castellino P: Oxidative stress and cellular stress response in diabetic nephropathy. Cell Stress Chaperones. 12:299–306. 2007. View Article : Google Scholar : PubMed/NCBI
40	Chernatynskaya AV, Looney B, Hu H, Zhu X and Xia CQ: Administration of recombinant human thioredoxin-1 significantly delays and prevents autoimmune diabetes in nonobese diabetic mice through modulation of autoimmunity. Diabetes Metab Res Rev. 27:809–812. 2011. View Article : Google Scholar : PubMed/NCBI
41	Gasdaska JR, Harney JW, Gasdaska PY, Powis G and Berry MJ: Regulation of Human Thioredoxin Reductase Expression and Activity by 3′-Untranslated Region Selenocysteine Insertion Sequence and mRNA Instability Elements. J Biol Chem. 274:25379–25385. 1999. View Article : Google Scholar : PubMed/NCBI
42	Rundlöf AK, Carlsten M and Arnér ESJ: The core promoter of human thioredoxin reductase 1: Cloning, transcriptional activity, and Oct-1, Sp1, and Sp3 binding reveal a housekeeping-type promoter for the AU-rich element-regulated gene. J Biol Chem. 276:30542–30551. 2001. View Article : Google Scholar : PubMed/NCBI