lncRNA uc.48+ regulates immune and inflammatory reactions mediated by the P2X7 receptor in type 2 diabetic mice

Abstract

Diabetes and non-coding RNAs are receiving increasing attention in contemporary medical research. The present study aimed to explore the role of the long non-coding RNA uc.48+ in the pathological changes of type 2 diabetes mellitus (T2DM) by observing the effects of uc.48+ small interfering RNA (siRNA) on the abdominal cells of a mouse model of T2DM. Mice with T2DM (DM group) were established by feeding with a high-sugar and-fat diet combined with intraperitoneal injections of low-dose streptozotocin. An intraperitoneal injection of uc.48+ siRNA was administered to the diabetic mice, and the serum levels of cytokines together with other clinical parameters, namely blood pressure, heart rate, mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were examined. Following the collection and identification of abdominal cells from the mice, the mRNA levels of uc.48+, mRNA and protein levels of the P2X 7 receptor, and phosphorylation levels of ERK1/2 were evaluated by reverse transcription-PCR and western blotting, respectively. The MWT and TWL were significantly decreased in the DM group compared with the non-diabetic control group. However, the reductions in MWT and TWL were significantly attenuated following uc.48+ siRNA injection. The systolic and diastolic blood pressure, as well as the serum levels of tumor necrosis factor α and interleukin 1β of mice in the DM group were significantly increased compared with those in the control group, whereas these changes were significantly attenuated following the injection of uc.48+ siRNA. In addition, the expression levels of P2X 7 receptor mRNA and protein, and the degree of phosphorylation of ERK1/2 in the abdominal cells were significantly increased in the DM group compared with the control group. These changes were also significantly attenuated following transfection with uc.48+ siRNA in vivo. In conclusion, these data suggest that uc.48+ may play an important role in the pathological changes of blood pressure, neurology and abdominal cell function in T2DM via interaction with the P2X 7 receptor.

Participation of lncRNAs in the development of diabetic complications: Systematic review and meta‐analysis. I. Rat

“…Because there is the possibility that some of the studies included in this article could consist of isolated cases, it is essential to compare them with other literature, therefore, in the case of MALAT1, 42,43 NONRATT021972, 44,45 NEAT1 46,47 and uc.48+. 48,49 In these studies, we can confirm that the main mechanisms identified are consistent across the lncRNAs reviewed.…”

Ultra-conserved RNA: a novel biological tool with diagnostic and therapeutic potential

“…Researchers found the silencing of these two ucRNAs could significantly reduce blood pressure, heart rate, and the ratio of low frequency to high frequency in heart rate variability, thus maintaining the dynamic balance between parasympathetic and sympathetic nerve activities [ 17 , 18 ]. Mechanistically, they also found low expression of uc.360 + and uc.48 + can alleviate diabetic cardiac autonomic neuropathy (DCAN) and pain caused by diabetes and promote cardiac autonomic nerve remodeling by reducing the expression of P2X4, P2X3, and P2X7 respectively, thus resulting in the reduction of the level of inflammatory factors and inhibition of the ERK1/2 signaling pathway [ 18 – 21 ]. In addition, uc.48 + induces mechanical hyperalgesia and pain transmission of trigeminal neuralgia (TN) by increasing the expression of P2X7 [ 22 ].…”

A novel definition and treatment of hyperinflammation in COVID-19 based on purinergic signalling

“…Upregulation of P2X7R on microglia coincides with increase of neuroinflammation after spinal cord injury. P2X7R of microglia participates in spinal cord-mediated neuroinflammation via regulating NLRP3 inflammasome-dependent inflammation [ 214 ] 113 Abdominal cells of male Kunming mice of clean grade Transfection of the long non-coding siRNA uc.48+ decreases the upregulated mRNA and protein levels of the P2X7 receptor in diabetes mellitus type 2 mice model [ 215 ] 114 Human embryonic kidney cells (HEK293T) Promotes paxillin and NLRP3 migration from the cytosol to the plasma membrane and facilitates P2X7R-paxillin interaction and PaxillinNLRP3 association, resulting in the formation of the P2X7R-Paxillin-NLRP3 complex. Paxillin is essential for ATP-induced NLRP3 inflammasome activation in mouse bone marrow-derived macrophages and bone marrow-derived dendritic cells (PMDCs) as well as in human PBMCs and THP-1-differentiated macrophages [ 216 ] 115 P2Y1R knockout, P2Y12R knockout, P2Y13R knockout, P2X7R knockout, NLRP3 knockout and wild type C57BL/6 mice Aggravates inflammatory bowel disease through ERK5-mediated tyrosine phosphorylation of the adaptor protein ASC essential for NLRP3 inflammasome activation and the secretion of IL-1β [ 217 ] 116 C57BL/6 mice: Wild-type, P2X7 knockout, NLRP3 knockout and caspase-1/11 knockout Induces the release of extracellular vesicles containing CD14.…”