Long non‑coding RNA FGD5‑AS1/microRNA‑133a‑3p upregulates aquaporin 1 to decrease the inflammatory response in LPS‑induced sepsis

Abstract

Sepsis is a systemic inflammatory response syndrome caused by infections. The present study aimed to investigate the potential mechanism of FGD5-AS1 in sepsis and lipopolysaccharide (LPS)-induced inflammatory response. An animal model of sepsis was constructed. LPS was used to induce mice HL-1 cardiomyocytes to construct a cell model. The association between FGD5-AS1 and miR-133a-3p was investigated through animal and cell models. FGD5-AS1 overexpression was used to analyze the effect of FGD5-AS1 on inflammatory reaction. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 levels were detected by enzyme-linked immunosorbent assay and reverse transcription-quantitative polymerase chain reaction. The interaction of FGD5-AS1, miR-133a-3p and aquaporin 1 (AQP1) was detected by dual-luciferase reporter assay and microRNA (miRNA/miR) pull-down assay. Compared with the control group, the expression of FGD5-AS1 was decreased and the expression of miR-133a-3p was increased in the sepsis group. FGD5-AS1 overexpression increased LPS-induced expression of FGD5-AS1 and AQP1, decreased the expression of miR-133a-3p, and inhibited the expression of the inflammatory cytokines, TNF-α, IL-6 and IL-1β. Dual-luciferase reporter and miRNA pull-down assays confirmed the interaction of FGD5-AS1, miR-133a-3p and AQP1. These results indicated that FGD5-AS1 is the competitive endogenous RNA of miR-133a-3p on AQP1, and thus FGD5-AS1 overexpression may be able to inhibit the inflammatory response in sepsis.

Revealing Landscape of Competing Endogenous RNA Networks in Sepsis-Induced Cardiovascular Diseases

“…The lncRNA-mediated ceRNA networks regulate cardiovascular toxicity in sepsis as shown in Tables 1 , 2 (Ref. [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ]).…”

“…Aquaporin protein 1 ( AQP1 ) acts as the target of miR-874 and is regulated by H19 . Moreover, AQP1 can be regulated by the lncRNA FGD5-AS1/miR-133a-3p axis in LPS-treated HL-1 cells, protecting cardiomyocytes from septic injury [ 26 ]. The upregulation of FGD5-AS1 increases the expression of AQP1 by downregulating miR-133a-3p expression.…”

ATP2B1-AS1 exacerbates sepsis-induced cell apoptosis and inflammation by regulating miR-23a-3p/TLR4 axis

“…For instance, lncRNA FGD5-AS1 attenuates inflammatory response via miR-133a-3p-dependent aquaporin-1 upregulation in lipopolysaccharide (LPS)-elicited sepsis. 10 LncRNA NEAT1 sponges miR-125 to downregulate mast cell expressed membrane protein 1 (MCEMP1) to inhibit immunity during sepsis. 11 LncRNA NKILA reduces cell viability and induces cell apoptosis, inflammation, and autophagy through miR-140-5p/CLDN2 axis in LPS-stimulated sepsis.…”