Abstract
Purpose
The aim of this study was to investigate the effects and possible mechanism of tea polyphenols (TPs) on the senescence of human glomerular mesangial cells (HGMCs) under high glucose conditions.
Methods
HGMCs were divided into the normal group (NG, 5.5 mmol/L glucose), mannitol group (MNT, 5.5 mmol/L glucose and 24.5 mmol/L mannitol), TP group (TP, 30 mmol/L glucose and 5 μg/mL TP) and high-dose d-glucose group (HG, 30 mmol/L glucose). The effects of TP on the cell morphology of HGMCs; the percentage of cells positive for senescence-associated β-galactosidase (SA-β-gal); the ratio of G1 phase of cell cycle; telomere length; and the expression of p-Akt, p53, p21 and Rb proteins of the Akt–p53–p21 signaling pathway and the expression miR-126 were examined.
Results
High glucose led to premature senescence of HGMCs, as evident from the increase in the percentage of SA-β-gal-positive cells, decrease in telomere length, cell cycle arrest at G1 phase,decrease in the expression of miR-126 and p-Akt and increase in the expression of p53, p21 and Rb proteins in the HG group. In contrast, in the TP group, these effects of high glucose treatment were abrogated and this indicates that TP had a protective effect on HGMCs.
Conclusions
High glucose induces the senescence of HGMCs in vitro via the miR-126 and Akt–p53–p21 signaling pathways. TP can delay the high glucose-induced senescence of HGMCs by regulating the activity of these signaling pathways. Thus, the polyphenols present in tea may have potential for the treatment of diabetic nephropathies associated with premature senescence.
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References
Kitada K, Nakano D, Ohsaki H, Hitomi H, Minamino T, Yatabe J, Felder RA, Mori H, Masaki T, Kobori H, Nishiyama A (2014) Hyperglycemia causes cellular senescence via a SGLT2- and p21-dependent pathway in proximal tubules in the early stage of diabetic nephropathy. J Diabetes Complicat 28(5):604–611. https://doi.org/10.1016/j.jdiacomp.2014.05.010
Zhu K, Kakehi T, Matsumoto M, Iwata K, Ibi M, Ohshima Y, Zhang J, Liu J, Wen X, Taye A, Fan C, Katsuyama M, Sharma K, Yabe-Nishimura C (2015) NADPH oxidase NOX1 is involved in activation of protein kinase C and premature senescence in early stage diabetic kidney. Free Radic Biol Med 83:21–30. https://doi.org/10.1016/j.freeradbiomed.2015.02.009
Verzola D, Gandolfo MT, Gaetani G, Ferraris A, Mangerini R, Ferrario F, Villaggio B, Gianiorio F, Tosetti F, Weiss U, Traverso P, Mji M, Deferrari G, Garibotto G (2008) Accelerated senescence in the kidneys of patients with type 2 diabetic nephropathy. Am J Physiol Renal Physiol 295(5):F1563–F1573. https://doi.org/10.1152/ajprenal.90302.2008
Sanders JL, Newman AB (2013) Telomere length in epidemiology: a biomarker of aging, age-related disease, both, or neither? Epidemiol Rev 35:112–131. https://doi.org/10.1093/epirev/mxs008
Feng C, Liu H, Yang M, Zhang Y, Huang B, Zhou Y (2016) Disc cell senescence in intervertebral disc degeneration: causes and molecular pathways. Cell Cycle 15(13):1674–1684. https://doi.org/10.1080/15384101.2016.1152433
Al-Kafaji G, Al-Mahroos G, Al-Muhtaresh HA, Skrypnyk C, Sabry MA, Ramadan AR (2016) Decreased expression of circulating microRNA-126 in patients with type 2 diabetic nephropathy: a potential blood-based biomarker. Exp Ther Med 12(2):815–822. https://doi.org/10.3892/etm.2016.3395
Caruana M, Vassallo N (2015) Tea polyphenols in Parkinson’s disease. Adv Exp Med Biol 863:117–137. https://doi.org/10.1007/978-3-319-18365-7_6
Lopez TE, Pham HM, Nguyen BV, Tahmasian Y, Ramsden S, Coskun V, Schriner SE, Jafari M (2016) Green tea polyphenols require the mitochondrial iron transporter, mitoferrin, for lifespan extension in Drosophila melanogaster. Arch Insect Biochem Physiol 93(4):210–221. https://doi.org/10.1002/arch.21353
Pakravan N, Mahmoudi E, Hashemi SA, Kamali J, Hajiaghayi R, Rahimzadeh M, Mahmoodi V (2017) Cosmeceutical effect of ethyl acetate fraction of Kombucha tea by intradermal administration in the skin of aged mice. J Cosmet Dermatol 17(6):1216–1224. https://doi.org/10.1111/jocd.12453
Qi G, Mi Y, Fan R, Zhao B, Ren B, Liu X (2017) Tea polyphenols ameliorates neural redox imbalance and mitochondrial dysfunction via mechanisms linking the key circadian regular Bmal1. Food Chem Toxicol Int J Publ Br Ind Biol Res Assoc 110:189–199. https://doi.org/10.1016/j.fct.2017.10.031
Molino S, Dossena M, Buonocore D, Ferrari F, Venturini L, Ricevuti G, Verri M (2016) Polyphenols in dementia: from molecular basis to clinical trials. Life Sci 161:69–77. https://doi.org/10.1016/j.lfs.2016.07.021
Maeda M, Hayashi T, Mizuno N, Hattori Y, Kuzuya M (2015) Intermittent high glucose implements stress-induced senescence in human vascular endothelial cells: role of superoxide production by NADPH oxidase. PLoS One 10(4):e0123169. https://doi.org/10.1371/journal.pone.0123169
Gurung RL, Yiamunaa M, Liu S, Liu JJ, Lim SC (2018) Short leukocyte telomere length predicts albuminuria progression in individuals with type 2 diabetes. Kidney Int Rep 3(3):592–601. https://doi.org/10.1016/j.ekir.2017.12.005
Wang W, Tan H, Liu H, Peng H, Li X, Dang X, He X (2018) Green tea polyphenols protect against preglomerular arteriopathy via the jagged1/notch1 pathway. Am J Transl Res 10(10):3276–3290
Qian Y, Zhang J, Fu X, Yi R, Sun P, Zou M, Long X, Zhao X (2018) Preventive effect of raw Liubao tea polyphenols on mouse gastric injuries induced by HCl/ethanol via anti-oxidative stress. Molecules. https://doi.org/10.3390/molecules23112848
Roh E, Kim JE, Kwon JY, Park JS, Bode AM, Dong Z, Lee KW (2017) Molecular mechanisms of green tea polyphenols with protective effects against skin photoaging. Crit Rev Food Sci Nutr 57(8):1631–1637. https://doi.org/10.1080/10408398.2014.1003365
Sur S, Panda CK (2017) Molecular aspects of cancer chemopreventive and therapeutic efficacies of tea and tea polyphenols. Nutrition 43–44:8–15. https://doi.org/10.1016/j.nut.2017.06.006
Heyza JR, Arora S, Zhang H, Conner KL, Lei W, Floyd AM, Deshmukh RR, Sarver J, Trabbic CJ, Erhardt P, Chan TH, Dou QP, Patrick SM (2018) Targeting the DNA repair endonuclease ERCC1-XPF with green tea polyphenol epigallocatechin-3-gallate (EGCG) and its prodrug to enhance cisplatin efficacy in human cancer cells. Nutrients. https://doi.org/10.3390/nu10111644
Onishi S, Ishino M, Kitazawa H, Yoto A, Shimba Y, Mochizuki Y, Unno K, Meguro S, Tokimitsu I, Miura S (2018) Green tea extracts ameliorate high-fat diet-induced muscle atrophy in senescence-accelerated mouse prone-8 mice. PLoS One 13(4):e0195753. https://doi.org/10.1371/journal.pone.0195753
Meng S, Cao JT, Zhang B, Zhou Q, Shen CX, Wang CQ (2012) Downregulation of microRNA-126 in endothelial progenitor cells from diabetes patients, impairs their functional properties, via target gene Spred-1. J Mol Cell Cardiol 53(1):64–72. https://doi.org/10.1016/j.yjmcc.2012.04.003
Acknowledgements
This study was supported by the Key Science and Technology Development Program of Nanjing City of the People’s Republic of China (YKK15056, YKK16097). This research was supported partly by the grant from National Natural Science Foundation of China (no. 81473684).
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Cao, D., Zhao, M., Wan, C. et al. Role of tea polyphenols in delaying hyperglycemia-induced senescence in human glomerular mesangial cells via miR-126/Akt–p53–p21 pathways. Int Urol Nephrol 51, 1071–1078 (2019). https://doi.org/10.1007/s11255-019-02165-7
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DOI: https://doi.org/10.1007/s11255-019-02165-7