title: LncRNA NONRATT021972 siRNA attenuates P2X7 receptor expression and inflammatory cytokine production induced by combined high glucose and free fatty acids in PC12 cells.
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 [Ca(2+)]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 [Ca(2+)]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.
authors: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
authors: Hong
authors: H
authors: Xu
authors: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
authors: Luling
authors: L
authors: He
authors: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
authors: Changle
authors: C
authors: Liu
authors: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
authors: Lan
authors: L
authors: Tang
authors: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
authors: Yonghu
authors: Y
authors: Xu
authors: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
authors: Mengqi
authors: M
authors: Xiong
authors: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
authors: Mei
authors: M
authors: Yang
authors: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
authors: Yongfang
authors: Y
authors: Fan
authors: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
authors: Fangfang
authors: F
authors: Hu
authors: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
authors: Xingzi
authors: X
authors: Liu
authors: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
authors: Lu
authors: L
authors: Ding
authors: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
authors: Yun
authors: Y
authors: Gao
authors: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
authors: Changshui
authors: C
authors: Xu
authors: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
authors: Guilin
authors: G
authors: Li
authors: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
authors: Shuangmei
authors: S
authors: Liu
authors: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
authors: Bing
authors: B
authors: Wu
authors: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
authors: Lifang
authors: L
authors: Zou
authors: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China. liangsd@hotmail.com.
authors: Shangdong
authors: S
authors: Liang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016207:Cytokines / Q000096:biosynthesis*; D003929:Diabetic Neuropathies / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000633:toxicity; D005786:Gene Expression Regulation / Q000235:genetics*; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000633:toxicity; D007118:Immunoassay; D016716:PC12 Cells; D062085:RNA, Long Noncoding / Q000378:metabolism*; D034741:RNA, Small Interfering; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D058486:Receptors, Purinergic P2X7 / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D005230:Fatty Acids, Nonesterified; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D058486:Receptors, Purinergic P2X7; C000611529:long non-coding RNA NONRATT021972, rat; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose
keywords: Diabetic neuropathy; High fatty acids; High glucose; Long noncoding RNA; P2X7 receptor; PC12 cell