Table of Contents Author Guidelines Submit a Manuscript
Mediators of Inflammation
Volume 2016 (2016), Article ID 3958453, 9 pages
http://dx.doi.org/10.1155/2016/3958453
Research Article

miR-146a Attenuates Inflammatory Pathways Mediated by TLR4/NF-κB and TNFα to Protect Primary Human Retinal Microvascular Endothelial Cells Grown in High Glucose

1Department of Anatomy and Cell Biology, Wayne State University, Detroit, MI 48201, USA
2Department of Ophthalmology, Wayne State University, Detroit, MI 48201, USA

Received 10 December 2015; Revised 29 January 2016; Accepted 31 January 2016

Academic Editor: Ulrich Eisel

Copyright © 2016 Eun-Ah Ye and Jena J. Steinle. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. A. Reddy, E. Zhang, and R. Natarajan, “Epigenetic mechanisms in diabetic complications and metabolic memory,” Diabetologia, vol. 58, no. 3, pp. 443–455, 2015. View at Publisher · View at Google Scholar
  2. R. L. Engerman and T. S. Kern, “Hyperglycemia as a cause of diabetic retinopathy,” Metabolism—Clinical and Experimental, vol. 35, no. 4, supplement 1, pp. 20–23, 1986. View at Google Scholar
  3. J. R. Nyengaard, Y. Ido, C. Kilo, and J. R. Williamson, “Interactions between hyperglycemia and hypoxia: implications for diabetic retinopathy,” Diabetes, vol. 53, no. 11, pp. 2931–2938, 2004. View at Publisher · View at Google Scholar · View at Scopus
  4. R. Klein, B. E. K. Klein, S. E. Moss, and K. J. Cruickshanks, “Relationship of hyperglycemia to the long-term incidence and progression of diabetic retinopathy,” Archives of Internal Medicine, vol. 154, no. 19, pp. 2169–2178, 1994. View at Publisher · View at Google Scholar · View at Scopus
  5. Q. Zhang, Y. Jiang, J. J. Toutounchian, C. Soderland, C. Ryan Yates, and J. J. Steinle, “Insulin-like growth factor binding protein-3 inhibits monocyte adhesion to retinal endothelial cells in high glucose conditions,” Molecular Vision, vol. 19, pp. 796–803, 2013. View at Google Scholar · View at Scopus
  6. E.-A. Ye and J. J. Steinle, “miR-15b/16 protects primary human retinal microvascular endothelial cells against hyperglycemia-induced increases in tumor necrosis factor alpha and suppressor of cytokine signaling 3,” Journal of Neuroinflammation, vol. 12, article 44, 2015. View at Publisher · View at Google Scholar
  7. Y. Jiang, Q. Zhang, C. Soderland, and J. J. Steinle, “TNFα and SOCS3 regulate IRS-1 to increase retinal endothelial cell apoptosis,” Cellular Signalling, vol. 24, no. 5, pp. 1086–1092, 2012. View at Publisher · View at Google Scholar · View at Scopus
  8. Y. Jiang, J. Pagadala, D. Miller, and J. J. Steinle, “Reduced insulin receptor signaling in retinal Müller cells cultured in high glucose,” Molecular Vision, vol. 19, pp. 804–811, 2013. View at Google Scholar · View at Scopus
  9. T. S. Devi, I. Lee, M. Hüttemann, A. Kumar, K. D. Nantwi, and L. P. Singh, “TXNIP links innate host defense mechanisms to oxidative stress and inflammation in retinal muller glia under chronic hyperglycemia: implications for diabetic retinopathy,” Experimental Diabetes Research, vol. 2012, Article ID 438238, 19 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  10. J. Halkein, S. P. Tabruyn, M. Ricke-Hoch et al., “MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy,” The Journal of Clinical Investigation, vol. 123, no. 5, pp. 2143–2154, 2013. View at Publisher · View at Google Scholar · View at Scopus
  11. K. Saito, K. Inagaki, T. Kamimoto et al., “MicroRNA-196a is a putative diagnostic biomarker and therapeutic target for laryngeal cancer,” PLoS ONE, vol. 8, no. 8, Article ID e71480, 2013. View at Publisher · View at Google Scholar · View at Scopus
  12. J. Feng, A. Li, J. Deng et al., “MiR-21 attenuates lipopolysaccharide-induced lipid accumulation and inflammatory response: potential role in cerebrovascular disease,” Lipids in Health and Disease, vol. 13, article 27, 2014. View at Publisher · View at Google Scholar · View at Scopus
  13. M. Bahadori, “New advances in RNAs,” Archives of Iranian Medicine, vol. 11, no. 4, pp. 435–443, 2008. View at Google Scholar · View at Scopus
  14. Y. Cao, B. Feng, S. Chen, Y. Chu, and S. Chakrabarti, “Mechanisms of endothelial to mesenchymal transition in the retina in diabetes,” Investigative Ophthalmology & Visual Science, vol. 55, no. 11, pp. 7321–7331, 2014. View at Publisher · View at Google Scholar · View at Scopus
  15. R. Mortuza, B. Feng, and S. Chakrabarti, “MiR-195 regulates SIRT1-mediated changes in diabetic retinopathy,” Diabetologia, vol. 57, no. 5, pp. 1037–1046, 2014. View at Publisher · View at Google Scholar · View at Scopus
  16. S. Fulzele, A. El-Sherbini, S. Ahmad et al., “MicroRNA-146b-3p regulates retinal inflammation by suppressing adenosine deaminase-2 in diabetes,” BioMed Research International, vol. 2015, Article ID 846501, 8 pages, 2015. View at Publisher · View at Google Scholar
  17. C. Cowan, C. K. Muraleedharan, J. J. O'Donnell et al., “MicroRNA-146 inhibits thrombin-induced NF-κB activation and subsequent inflammatory responses in human retinal endothelial cells,” Investigative Ophthalmology & Visual Science, vol. 55, no. 8, pp. 4944–4951, 2014. View at Publisher · View at Google Scholar · View at Scopus
  18. Y. Li, T. G. VandenBoom II, Z. Wang et al., “Abstract 5703: up-regulation of miR-146a contributes to the inhibition of invasion of pancreatic cancer cells,” Cancer Research, vol. 70, article 5703, 2010. View at Publisher · View at Google Scholar
  19. M. A. Nahid, M. Satoh, and E. K. Chan, “Mechanistic role of microRNA-146a in endotoxin-induced differential cross-regulation of TLR signaling,” The Journal of Immunology, vol. 186, no. 3, pp. 1723–1734, 2011. View at Publisher · View at Google Scholar
  20. M. R. Rippo, F. Olivieri, V. Monsurrò, F. Prattichizzo, M. C. Albertini, and A. D. Procopio, “MitomiRs in human inflamm-aging: a hypothesis involving miR-181a, miR-34a and miR-146a,” Experimental Gerontology, vol. 56, pp. 154–163, 2014. View at Publisher · View at Google Scholar · View at Scopus
  21. Q. Wang, S. N. Bozack, Y. Yan, M. E. Boulton, M. B. Grant, and J. V. Busik, “Regulation of retinal inflammation by rhythmic expression of miR-146a in diabetic Retina,” Investigative Ophthalmology & Visual Science, vol. 55, no. 6, pp. 3986–3994, 2014. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Balasubramanyam, S. Aravind, K. Gokulakrishnan et al., “Impaired miR-146a expression links subclinical inflammation and insulin resistance in Type 2 diabetes,” Molecular and Cellular Biochemistry, vol. 351, no. 1-2, pp. 197–205, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. R. Lenin, A. Sankaramoorthy, V. Mohan, and M. Balasubramanyam, “Altered immunometabolism at the interface of increased endoplasmic reticulum (ER) stress in patients with type 2 diabetes,” Journal of Leukocyte Biology, vol. 98, no. 4, pp. 615–622, 2015. View at Publisher · View at Google Scholar
  24. J. R. van Beijnum, W. A. Buurman, and A. W. Griffioen, “Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1),” Angiogenesis, vol. 11, no. 1, pp. 91–99, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. X.-L. Chen, X.-D. Zhang, Y.-Y. Li, X.-M. Chen, D.-R. Tang, and R.-J. Ran, “Involvement of HMGB1 mediated signalling pathway in diabetic retinopathy: evidence from type 2 diabetic rats and ARPE-19 cells under diabetic condition,” The British Journal of Ophthalmology, vol. 97, no. 12, pp. 1598–1603, 2013. View at Publisher · View at Google Scholar · View at Scopus
  26. H. Mudaliar, C. Pollock, J. Ma, H. Wu, S. Chadban, and U. Panchapakesan, “The role of TLR2 and 4-mediated inflammatory pathways in endothelial cells exposed to high glucose,” PLoS ONE, vol. 9, no. 10, Article ID e108844, 2014. View at Publisher · View at Google Scholar · View at Scopus
  27. Y. L. Wang, K. Wang, S. J. Yu et al., “Association of the TLR4 signaling pathway in the retina of streptozotocin-induced diabetic rats,” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 253, no. 3, pp. 389–398, 2015. View at Publisher · View at Google Scholar
  28. K. D. Taganov, M. P. Boldin, K.-J. Chang, and D. Baltimore, “NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 33, pp. 12481–12486, 2006. View at Publisher · View at Google Scholar · View at Scopus
  29. A. Yoshida, S. Yoshida, T. Ishibashi, M. Kuwano, and H. Inomata, “Suppression of retinal neovascularization by the NF-kappaB inhibitor pyrrolidine dithiocarbamate in mice,” Investigative Ophthalmology & Visual Science, vol. 40, no. 7, pp. 1624–1629, 1999. View at Google Scholar · View at Scopus
  30. L. Su, J. Ji, J. Bian, Y. Fu, Y. Ge, and Z. Yuan, “Tacrolimus (FK506) prevents early retinal neovascularization in streptozotocin-induced diabetic mice,” International Immunopharmacology, vol. 14, no. 4, pp. 606–612, 2012. View at Publisher · View at Google Scholar · View at Scopus
  31. R. A. Kowluru, J. M. Santos, and Q. Zhong, “Sirt1, A negative regulator of matrix metalloproteinase-9 in diabetic retinopathy,” Investigative Ophthalmology and Visual Science, vol. 55, no. 9, pp. 5653–5660, 2014. View at Publisher · View at Google Scholar · View at Scopus
  32. R. A. Kowluru, P. Koppolu, S. Chakrabarti, and S. Chen, “Diabetes-induced activation of nuclear transcriptional factor in the retina, and its inhibition by antioxidants,” Free Radical Research, vol. 37, no. 11, pp. 1169–1180, 2003. View at Publisher · View at Google Scholar · View at Scopus
  33. H. S. Cheng, N. Sivachandran, A. Lau et al., “Combined mutation of Vhl and Trp53 causes renal cysts and tumours in mice,” EMBO Molecular Medicine, vol. 5, no. 6, pp. 949–966, 2013. View at Publisher · View at Google Scholar
  34. D. Wu, C. Cerutti, M. A. Lopez-Ramirez et al., “Brain endothelial miR-146a negatively modulates T-cell adhesion through repressing multiple targets to inhibit NF-κB activation,” Journal of Cerebral Blood Flow & Metabolism, vol. 35, no. 3, pp. 412–423, 2015. View at Publisher · View at Google Scholar
  35. Z. Kanaan, R. Barnett, S. Gardner et al., “Differential microRNA (miRNA) expression could explain microbial tolerance in a novel chronic peritonitis model,” Innate Immunity, vol. 19, no. 2, pp. 203–212, 2013. View at Publisher · View at Google Scholar · View at Scopus
  36. U. Rajamani and I. Jialal, “Hyperglycemia induces toll-like receptor-2 and -4 expression and activity in human microvascular retinal endothelial cells: implications for diabetic retinopathy,” Journal of Diabetes Research, vol. 2014, Article ID 790902, 15 pages, 2014. View at Publisher · View at Google Scholar · View at Scopus
  37. M. P. Boldin, K. D. Taganov, D. S. Rao et al., “miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice,” Journal of Experimental Medicine, vol. 208, no. 6, pp. 1189–1201, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. R. Saba, D. L. Sorensen, and S. A. Booth, “MicroRNA-146a: a dominant, negative regulator of the innate immune response,” Frontiers in Immunology, vol. 5, article 578, 2014. View at Publisher · View at Google Scholar · View at Scopus
  39. R. J. Chen, H. H. Yuan, T. Y. Zhang et al., “Heme oxygenase-2 suppress TNF-α and IL6 expression via TLR4/MyD88-dependent signaling pathway in mouse cerebral vascular endothelial cells,” Molecular Neurobiology, vol. 50, no. 3, pp. 971–978, 2014. View at Publisher · View at Google Scholar
  40. N. Sharma, R. Verma, K. L. Kumawat, A. Basu, and S. K. Singh, “miR-146a suppresses cellular immune response during Japanese encephalitis virus JaOArS982 strain infection in human microglial cells,” Journal of Neuroinflammation, vol. 12, article 30, 2015. View at Publisher · View at Google Scholar
  41. S.-X. Gu, X. Li, J. L. Hamilton et al., “MicroRNA-146a reduces IL-1 dependent inflammatory responses in the intervertebral disc,” Gene, vol. 555, no. 2, pp. 80–87, 2015. View at Publisher · View at Google Scholar · View at Scopus
  42. R. K. Kutty, C. N. Nagineni, W. Samuel et al., “Differential regulation of microRNA-146a and microRNA-146b-5p in human retinal pigment epithelial cells by interleukin-1β, tumor necrosis factor-α, and interferon-γ,” Molecular Vision, vol. 19, pp. 737–750, 2013. View at Google Scholar
  43. G. Li, C. Luna, J. Qiu, D. L. Epstein, and P. Gonzalez, “Modulation of inflammatory markers by miR-146a during replicative senescence in trabecular meshwork cells,” Investigative Ophthalmology & Visual Science, vol. 51, no. 6, pp. 2976–2985, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. R. A. Kowluru, A. Kowluru, and M. Kanwar, “Small molecular weight G-protein, H-Ras, and retinal endothelial cell apoptosis in diabetes,” Molecular and Cellular Biochemistry, vol. 296, no. 1-2, pp. 69–76, 2007. View at Publisher · View at Google Scholar · View at Scopus
  45. Y. Du, M. A. Smith, C. M. Miller, and T. S. Kern, “Diabetes-induced nitrative stress in the retina, and correction by aminoguanidine,” Journal of Neurochemistry, vol. 80, no. 5, pp. 771–779, 2002. View at Publisher · View at Google Scholar · View at Scopus
  46. Y. Du, C. M. Miller, and T. S. Kern, “Hyperglycemia increases mitochondrial superoxide in retina and retinal cells,” Free Radical Biology and Medicine, vol. 35, no. 11, pp. 1491–1499, 2003. View at Publisher · View at Google Scholar · View at Scopus
  47. B. Feng, S. Chen, K. McArthur et al., “miR-146a-mediated extracellular matrix protein production in chronic diabetes complications,” Diabetes, vol. 60, no. 11, pp. 2975–2984, 2011. View at Publisher · View at Google Scholar · View at Scopus
  48. Y. Huang, Y. Liu, L. Li et al., “Involvement of inflammation-related miR-155 and miR-146a in diabetic nephropathy: implications for glomerular endothelial injury,” BMC Nephrology, vol. 15, article 142, 2014. View at Publisher · View at Google Scholar · View at Scopus
  49. B. Kovacs, S. Lumayag, C. Cowan, and S. Xu, “microRNAs in early diabetic retinopathy in streptozotocin-induced diabetic rats,” Investigative Ophthalmology & Visual Science, vol. 52, no. 7, pp. 4402–4409, 2011. View at Publisher · View at Google Scholar · View at Scopus
  50. S. Yang, L. Xu, T. Yang, and F. Wang, “High-mobility group box-1 and its role in angiogenesis,” Journal of Leukocyte Biology, vol. 95, no. 4, pp. 563–574, 2014. View at Publisher · View at Google Scholar · View at Scopus
  51. Y. Chen, F. Qiao, Y. Zhao, Y. Wang, and G. Liu, “HMGB1 is activated in type 2 diabetes mellitus patients and in mesangial cells in response to high glucose,” International Journal of Clinical and Experimental Pathology, vol. 8, no. 6, pp. 6683–6691, 2015. View at Google Scholar
  52. A. R. C. Santos, G. Dvoriantchikova, Y. Li et al., “Cellular mechanisms of high mobility group 1 (HMGB-1) protein action in the diabetic retinopathy,” PLoS ONE, vol. 9, no. 1, Article ID e87574, 2014. View at Publisher · View at Google Scholar · View at Scopus
  53. C. J. d'Adhemar, C. D. Spillane, M. F. Gallagher et al., “The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer,” PLoS ONE, vol. 9, no. 6, Article ID e100816, 2014. View at Publisher · View at Google Scholar · View at Scopus
  54. J. Dubbert, A. Bowers, Y. Su, and D. McClenahan, “Effect of TRIF on permeability and apoptosis in bovine microvascular endothelial cells exposed to lipopolysaccharide,” Veterinary Journal, vol. 198, no. 2, pp. 419–423, 2013. View at Publisher · View at Google Scholar · View at Scopus
  55. R. Miyata, T. Kakuki, K. Nomura et al., “Poly(I:C) induced microRNA-146a regulates epithelial barrier and secretion of proinflammatory cytokines in human nasal epithelial cells,” European Journal of Pharmacology, vol. 761, pp. 375–382, 2015. View at Publisher · View at Google Scholar
  56. D. Bhaumik, G. K. Scott, S. Schokrpur, C. K. Patil, J. Campisi, and C. C. Benz, “Expression of microRNA-146 suppresses NF-κB activity with reduction of metastatic potential in breast cancer cells,” Oncogene, vol. 27, no. 42, pp. 5643–5647, 2008. View at Publisher · View at Google Scholar · View at Scopus
  57. J. Qiu, M. Nishimura, Y. Wang et al., “Early release of HMGB-1 from neurons after the onset of brain ischemia,” Journal of Cerebral Blood Flow and Metabolism, vol. 28, no. 5, pp. 927–938, 2008. View at Publisher · View at Google Scholar · View at Scopus