PVT1 regulates inflammation and cardiac function via the MAPK/NF‑κB pathway in a sepsis model

Abstract

The aim of the present study was to investigate the role of plasmacytoma variant translocation gene 1 (PVT1) in the occurrence and development of sepsis-induced inflammation and cardiac dysfunction and its underlying mechanism. A sepsis rat model was first established by cecal ligation and puncture. The mRNA levels of PVT1 and microRNA-143 in the myocardial tissues of rats were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. Cardiac function, levels of myocardial injury markers and inflammatory indicators were detected following PVT1 knockdown. The regulatory effect of microRNA-143 on PVT1 was assessed using a luciferase reporter gene assay and RT-qPCR analysis. The specific role of PVT1 in regulating the mitogen-activated protein kinase (MAPK)/nuclear factor (NF)-κB pathway was detected using western blot analysis. PVT1 was downregulated and microRNA-143 was upregulated in the myocardial tissues of sepsis rats. The left ventricular peak pressure was markedly decreased in the sepsis rats. By contrast, the left ventricular end diastolic pressure, levels of inflammatory indicators, myocardial injury markers and complement proteins of C5 and C5a were increased in the sepsis rats. The above changes were reversed by PVT1 knockdown or the upregulation of microRNA-143. MicroRNA-143 was confirmed as being bound to PVT1 using the luciferase reporter gene assay and RT-qPCR analysis. Upregulated PVT1 was capable of activating the MAPK/NF-κB pathway. Taken together, PVT1 was upregulated in the myocardial tissues of sepsis rats, which inhibited cardiac function and promoted the secretion of inflammatory factors; and the mechanism was associated with the MAPK/NF-κB pathway.

Upregulated lncRNA Pvt1 may be important for cardiac remodeling at the infarct border zone

“…This requires confirmation from further studies. a previous study has demonstrated that Pvt1 was upregulated in the myocardial tissues of sepsis rats, which inhibited cardiac function and promoted the secretion of inflammatory factors via activation of the MaPK/nF-κB pathway (48). Furthermore, Pvt1 has also previously been demonstrated to be upregulated in cardiac hypertrophic model mice when compared with the sham group; while knockout of Pvt1 by siRNA significantly reduced the cardiomyocyte size (49).…”

Knockdown of lncRNA PVT1 alleviates high glucose-induced proliferation and fibrosis in human mesangial cells by miR-23b-3p/WT1 axis

“…In the present study, our data substantiated that the NF-κB signaling pathway was involved in the regulation of the PVT1/miR-23b-3p/WT1 axis in HG-induced MCs. Feng et al demonstrated that PVT1 modulated inflammatory response and cardiac function in a sepsis model through regulating the NF-κB signaling pathway [37]. Naidu et al discovered that miR-23b mediated the regulation in lung tumorigenesis via targeting the NF-κB signaling pathway [38].…”

Knockdown of exosome‑mediated lnc‑PVT1 alleviates lipopolysaccharide‑induced osteoarthritis progression by mediating the HMGB1/TLR4/NF‑κB pathway via miR‑93‑5p

“…PVT1 has been revealed to accelerate lipopolysaccharide (lPS)-induced septic acute kidney injury (11). PVT1 was demonstrated to impede cardiac function and facilitate the secretion of inflammatory factors in a sepsis model (12). additionally, PVT1 has been revealed to modulate the apoptosis of chondrocytes in osteoarthritis (13).…”