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LncRNA NONRATT021972 siRNA attenuates P2X7 receptor expression and inflammatory cytokine production induced by combined high glucose and free fatty acids in PC12 cells

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Abstract

Diabetic neuropathy (DNP) is a frequent chronic complication of diabetes mellitus with potentially life-threatening outcomes. High glucose and elevated free fatty acids (FFAs) have been recently recognized as major causes of nervous system damage in diabetes. Our previous study has indicated extracellular stimuli, such as high glucose and/or FFA stress, may activate the p38 mitogen-activated protein kinase (MAPK) signaling pathway and induce a p38 MAPK-dependent sensitization of the P2X7 receptor and release of inflammatory factors in PC12 cells, while the mechanisms underlying remain to be elucidated. Long noncoding RNAs (lncRNAs) play important roles in diverse biological processes, including activation of a series of pathway signalings. Here, we showed combined high d-glucose and FFAs (HGHF) induced an increment of lncRNA-NONRATT021972 (NONCODE ID, nc021972) in PC12 cells. Nc021972 small interference RNA (siRNA) alleviated HGHF-induced activation of p38 MAPK, expression of the P2X7 receptor, and [Ca2+]i increment upon P2X7 receptor activation. Further experiments showed that there existed a crosstalk between nc021972 and the p38 MAPK signaling pathway. Inhibition of p38 MAPK signaling decreased nc021972-induced expression of the P2X7 receptor and [Ca2+]i increment upon P2X7 receptor activation. Also, nc021972 siRNA inhibited HGHF-induced PC12 release of TNF-α and IL-6 and rescued decreased cell viability mediated by the P2X7 receptor. Therefore, inhibition of nc021972 may serve as a novel therapeutic strategy for diabetes complicated with nervous inflammatory diseases.

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Acknowledgments

This work was supported by grants (nos. 81171184,81360140,81360136,81570735,81560219, 81302501 and 81560529) from the National Natural Science Foundation of China, grants (nos. 20151BBG70249, 20132BAB215005, and 20122BAB215005) from the Natural Science Foundation of Jiangxi Province, a grant (nos. GJJ14093 and GJJ14319) from the Education Department of Jiangxi Province, a grant (no. 20155643) from the Foundation of the Health Department of Jiangxi Province, and grants (nos. 201410403132, 201510403039, YC2015-S041, 20140611, 2015195 and 14001840) from the Nanchang University Students’ Innovation and Entrepreneurship Training Program.

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Authors and Affiliations

  1. Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China

    Hong Xu, Luling He, Changle Liu, Lan Tang, Yonghu Xu, Mengqi Xiong, Mei Yang, Yongfang Fan, Fangfang Hu, Xingzi Liu, Lu Ding, Yun Gao, Changshui Xu, Guilin Li, Shuangmei Liu, Bing Wu, Lifang Zou & Shangdong Liang

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  1. Hong Xu
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Correspondence to Shangdong Liang.

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Xu, H., He, L., Liu, C. et al. LncRNA NONRATT021972 siRNA attenuates P2X7 receptor expression and inflammatory cytokine production induced by combined high glucose and free fatty acids in PC12 cells. Purinergic Signalling 12, 259–268 (2016). https://doi.org/10.1007/s11302-016-9500-0

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