Exp Clin Endocrinol Diabetes 2022; 130(01): 30-36
DOI: 10.1055/a-1185-9283
Article

Knock-Down of Long Non-Coding RNA ANRIL Suppresses Mouse Mesangial Cell Proliferation, Fibrosis, Inflammation via Regulating Wnt/β-Catenin and MEK/ERK Pathways in Diabetic Nephropathy

Xun Fang
1   Department of Nephrology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
,
Jun Hu
2   Department of Gerontology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
,
Hongyan Zhou
3   Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
› Author Affiliations

Abstract

Aims Our study aimed to investigate the role of long non-coding RNA ANRIL (lnc-ANRIL) knock-down in regulating cell activities, inflammation and downstream signaling pathways in mouse mesangial cellular diabetic nephropathy (DN) model.

Methods The mouse mesangial cells (SV40-MES13 cells) were treated with high-glucose (HG) to construct cellular DN model. Lnc-ANRIL knock-down plasmid and control knock-down plasmid were transfected into HG-treated SV40-MES13 cells as Sh-ANRIL group and Sh-NC group respectively.

Results Lnc-ANRIL expression was significantly higher in HG-treated SV40-MES13 cells compared with normal glucose-treated SV40-MES13 cells and osmotic control-treated SV40-MES13 cells. Lnc-ANRIL knock-down suppressed cell proliferation and promoted cell apoptosis in HG-treated SV40-MES13 cells. As for fibrosis, lnc-ANRIL knock-down reduced fibronectin and collagen I expressions in HG-treated SV40-MES13 cells. Besides, the expressions of supernatant tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-1β, IL-6, IL-8 and IL-18 were reduced in Sh-ANRIL group compared with Sh-NC group. Furthermore, Wnt3, β-catenin, p-MEK1 and p-ERK1 expressions were suppressed in Sh-ANRIL group compared with Sh-NC group, which suggested that lnc-ANRIL knock-down inhibited Wnt/β-catenin and MEK/ERK pathways in HG-treated SV40-MES13 cells.

Conclusions Lnc-ANRIL knock-down suppresses mouse mesangial cell proliferation, fibrosis, inflammation, Wnt/β-catenin and MEK/ERK pathways in DN.



Publication History

Received: 27 March 2020
Received: 12 May 2020

Accepted: 22 May 2020

Article published online:
29 July 2020

© 2020. Thieme. All rights reserved.

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  • References

  • 1 Kopel J, Pena-Hernandez C, Nugent K. Evolving spectrum of diabetic nephropathy. World J Diabetes 2019; 10: 269-279
  • 2 Fineberg D, Jandeleit-Dahm KA, Cooper ME. Diabetic nephropathy: diagnosis and treatment. Nat Rev Endocrinol 2013; 9: 713-723
  • 3 Gu HF. Genetic and epigenetic studies in diabetic kidney disease. Front Genet 2019; 10: 507
  • 4 Kato M, Natarajan R. Diabetic nephropathy–emerging epigenetic mechanisms. Nat Rev Nephrol 2014; 10: 517-530
  • 5 Thomas MC. Epigenetic mechanisms in diabetic kidney disease. Curr Diab Rep 2016; 16: 31
  • 6 Yu F, Pang G, Zhao G. ANRIL acts as onco-lncRNA by regulation of microRNA-24/c-Myc, MEK/ERK and Wnt/beta-catenin pathway in retinoblastoma. Int J Biol Macromol 2019; 128: 583-592
  • 7 Wu JH, Tang JM, Li J. et al. Upregulation of SOX2-activated lncRNA ANRIL promotes nasopharyngeal carcinoma cell growth. Sci Rep 2018; 8: 3333
  • 8 Zhang L, Wang YM. Expression and function of lncRNA ANRIL in a mouse model of acute myocardial infarction combined with type 2 diabetes mellitus. J Chin Med Assoc 2019; 82: 685-692
  • 9 Feng X, Zhao J, Ding J. et al. LncRNA Blnc1 expression and its effect on renal fibrosis in diabetic nephropathy. Am J Transl Res 2019; 11: 5664-5672
  • 10 Zhang P, Sun Y, Peng R. et al. Long non-coding RNA Rpph1 promotes inflammation and proliferation of mesangial cells in diabetic nephropathy via an interaction with Gal-3. Cell Death Dis 2019; 10: 526
  • 11 Thomas AA, Feng B, Chakrabarti S. ANRIL regulates production of extracellular matrix proteins and vasoactive factors in diabetic complications. Am J Physiol Endocrinol Metab 2018; 314: E191-E200
  • 12 Wei JC, Shi YL, Wang Q. LncRNA ANRIL knockdown ameliorates retinopathy in diabetic rats by inhibiting the NF-kappaB pathway. Eur Rev Med Pharmacol Sci 2019; 23: 7732-7739
  • 13 Miller CG, Pozzi A, Zent R. et al. Effects of high glucose on integrin activity and fibronectin matrix assembly by mesangial cells. Mol Biol Cell 2014; 25: 2342-2350
  • 14 Huang D, Bi C, Zhao Q. et al. Knockdown long non-coding RNA ANRIL inhibits proliferation, migration and invasion of HepG2 cells by down-regulation of miR-191. BMC Cancer 2018; 18: 919
  • 15 Lin CL, Wang JY, Huang YT. et al. Wnt/beta-catenin signaling modulates survival of high glucose-stressed mesangial cells. J Am Soc Nephrol 2006; 17: 2812-2820
  • 16 Liang D, Song Z, Liang W. et al. Metformin inhibits TGF-beta 1-induced MCP-1 expression through BAMBI-mediated suppression of MEK/ERK1/2 signalling. Nephrology (Carlton) 2019; 24: 481-488
  • 17 Li N, Wang LJ, Xu WL. et al. MicroRNA3795p suppresses renal fibrosis by regulating the LIN28/let7 axis in diabetic nephropathy. Int J Mol Med 2019; 44: 1619-1628
  • 18 Xiong Y, Zhou L. The signaling of cellular senescence in diabetic nephropathy. Oxid Med Cell Longev 2019; 2019: 7495629
  • 19 Han F, Xue M, Chang Y. et al. Triptolide suppresses glomerular mesangial cell proliferation in diabetic nephropathy is associated with inhibition of PDK1/Akt/mTOR pathway. Int J Biol Sci 2017; 13: 1266-1275
  • 20 Sathishkumar C, Prabu P, Mohan V. et al. Linking a role of lncRNAs (long non-coding RNAs) with insulin resistance, accelerated senescence, and inflammation in patients with type 2 diabetes. Hum Genomics 2018; 12: 41
  • 21 Thomas AA, Feng B, Chakrabarti S. ANRIL: A regulator of VEGF in diabetic retinopathy. Invest Ophthalmol Vis Sci 2017; 58: 470-480
  • 22 Yang J, Chen L, Ding J. et al. MicroRNA-24 inhibits high glucose-induced vascular smooth muscle cell proliferation and migration by targeting HMGB1. Gene 2016; 586: 268-273
  • 23 Zhao J, Sun H, Zhang JM. et al. Long non-coding RNA ANRIL down-regulates microRNA-7 to protect human trabecular meshwork cells in an experimental model for glaucoma. Eur Rev Med Pharmacol Sci 2019; 23: 3173-3182