GATA1 regulates the microRNA‑328‑3p/PIM1 axis via circular RNA ITGB1 to promote renal ischemia/reperfusion injury in HK‑2 cells

Abstract

Acute kidney injury (AKI) is caused by renal ischemia/reperfusion injury (IRI) during kidney transplantation. The levels of both circular RNAs (circRNAs) and microRNAs (miRNAs/miR) appear to be critical for AKI detection. While several RNA interactions in AKI have been found, the regulatory mechanisms between the molecules remain to be fully elucidated. In the present study, miRNA expression profiling analysis was conducted using an online dataset to identify the differentially expressed miRNAs in rats with IRI. miR-328-3p was also found to be downregulated in human kidney-2 (HK-2) cells subjected to hypoxia/reperfusion (H/R), and its overexpression targeting pim-1 proto-oncogene (PIM1) resulted in an increased viability and a reduced apoptosis, as well as in the decreased expression of inflammatory factors upon H/R exposure. Putative targets and circRNAs of miR-328-3p were identified using publically available databases. The inhibition of circRNA integrin beta 1 (ITGB1; circITGB1) suppressed the inflammatory response induced by H/R by sponging miR-328-3p in HK-2 cells. Furthermore, a sequence of the functional ITGB1 promoter was studied for transcription factor GATA binding protein 1 (GATA1) binding sites. GATA1 binds to the ITGB1 promoter, leading to the expression of circITGB1. On the whole, the findings of the present study revealed a regulatory pathway modulating miR-328-3p in IRI, demonstrating that the GATA1-mediated regulation of circITGB1 enhanced the H/R-induced inflammatory response via the miR-328-3p/PIM1 axis.

Screening and identification of key biomarkers in diabetic kidney disease and its complications: Evidence from bioinformatics and next generation sequencing data analysis

“…In the current investigation, integrated bioinformatics methods assisted in an analysis of how key genes change in their expression to uncover potential DKD based on NGS dataset (GSE217709), and we identified total 958 DEGs, including 479 up regulated genes and 479 down regulated genes. [115], FGFR2 [116], ROR2 [117], RTN1 [118], NOTCH3 [119], JAK3 [120], IL18 [121], COL4A1 [122], CEBPD (CCAAT enhancer binding protein delta) [123], KIF26B [124], HES1 [125], CBS (cystathionine beta-synthase) [126], EGF (epidermal growth factor) [127], TRPM2 [128], HSPG2 [129], NOX4 [130], MYH9 [131], GLIS2 [132], TRPV4 [133], GSN (gelsolin) [134], DUSP2 [135], LRP5 [136], CD248 [137], GLI1 [138], PIM1 [139], TGFB3 [140], MDK (midkine) [141], TRPC6 [142], NKD2 [143], NUAK1 [144], CYS1 [145], POSTN (periostin) [146], STAT4 [147], AEBP1 [148] and NNMT (nicotinamide N-methyltransferase) [149] might be a possible genetic markers for susceptibility to renal fibrosis. MMP12 [150], BMP2 [151], IL33 [152], SORCS1 [153], IRF4 [154], PENK (proenkephalin) [77], mellitus.…”

miR-208a-3p regulated by circUQCRC2 suppresses ischemia/reperfusion-induced acute kidney injury by inhibiting CELF2-mediated tubular epithelial cell apoptosis, inflammation and ferroptosis

“…An immortalized proximal tubule epithelial cell line HK-2 was acquired from the National Collection of Authenticated Cell Cultures (Shanghai, China) and cultured in DMEM/F12 containing 10% fetal bovine serum (Gibco, Grand Island, NY, USA), 100 U/mL penicillin, and 100 μg/mL streptomycin under 5% CO 2 and 95% air atmosphere at 37°C. H/R injury of HK-2 cells was induced according to previously described (34). Briefly, HK-2 cells were incubated in glucose- and serum-free culture medium for 12 h under hypoxic conditions (1% O 2 , 94% N 2 , and 5% CO 2 ).…”

The role of non-protein-coding RNAs in ischemic acute kidney injury

“…The target of miR-328-3p is the Pim-1 proto-oncogene (PIM1), and its overexpression led to an increase in cell viability and a decrease in apoptosis, as well as a decrease in the expression of inflammatory factors following HR exposure. In addition, the functional ITGB1 promoter sequence contains a binding site for the transcription factor GATA binding protein 1 (GATA1), which promotes the expression of circITGB1( 157 ).…”