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Lnc453774.1 mediated gene expression in human HK-2 cells

ABSTRACT: Long noncoding RNAs (lncRNAs) have been proposed to be engaged in the pathogenesis of renal fibrosis. The current study aims to determine the role of lnc453774.1 in the development of renal fibrosis and its underlying mechanism.Transforming growth factor-β1 (TGF-β1)-induced cell model of renal fibrosis was constructed. RNA sequencing was performed to identify DEGs targeted by lnc453774.1 in TGF-β1-induced renal fibrosis. Dataset GSE23338 was adopted to identify DEGs in 48 h TGF-β1-stimuated human kidney epithelial cells, and these DEGs were interested with genes in the key module using a WGCNA to generate key genes associated with renal fibrosis. Miranda software was adopted to predict miRs that have targeting relationship with keys genes and lnc453774.1, and key genes that have targeting relationship with these miRs were regarded as important genes. A PPI network among lnc453774.1, important genes and reported genes related to autophagy, oxidative stress, and cell adhesion was constructed to select key target genes by lnc453774.1. Twenty key genes regulated by lnc453774.1 was yielded by intersecting genes in key module (turquoise) and dataset GSE23338. Fourteen miRs have targeting relationship with lnc453774.1 and key genes, and 8 important genes targeted by these 14 miRs were identified. FBN1, IGF1R and KLF7 were identified to be associated with autophagy, oxidative stress, and cell adhesion and were upregulated in the lnc453774.1-overexpressing in TGF-β1-induced cells. These results show FBN1, IGF1R and KLF7 serve as downstream targets of lnc453774.1 and protect against renal fibrosis by regulating autophagy, oxidative stress, and cell adhesion.

ORGANISM(S): Homo sapiens

PROVIDER: GSE168559 | GEO | 2021/03/10

REPOSITORIES: GEO

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Project description:We aimed to identify miRNA biomarkers of renal injury in kidney biopsies from patients with lupus nephritis. MiRNA profiles of 8 patients were analyzed for correlation with various clinical features including Progression, Activity, Chronicity, and Time to Kidney Failure. MicroRNAs (miRs) are promising biomarkers and are involved in pathogenesis of kidney diseases. We aimed to identify miR biomarkers of renal injury in kidney biopsies from patients with lupus nephritis and study their potential role in renal fibrosis. miR-150 was significantly increased in kidneys with high chronicity compared to low chronicity and it correlated positively with chronicity index scores and renal collagen I expression. In kidneys with high chronicity, miR-150 was found predominantly in proximal tubular cells (PTCs) and was moderately expressed in podocytes and to lesser degree in mesangial cells (MCs). We hypothesized that miR-150 increases fibrosis by downregulating a negative regulator of profibrotic proteins. Suppressor of cytokine signaling1 (SOCS1) is a predicted target of miR-150 and has shown antifibrotic role. After confirming that SOCS1 is a direct target of miR-150, we showed that transfection of a miR-150 analog downregulated SOCS1 protein and upregulated the profibrotic proteins fibronectin, collagen I, collagen III, and TGF-β1 in both primary normal human renal PTCs and MCs. A similar effect was seen when using a SOCS1 siRNA to confirm that the effect of miR-150 on profibrotic proteins is mediated through SOCS1. Stimulation with TGF-β1 induced miR-150 increase in PTCs and human podocytes but not MCs. These results suggest that miR-150 might be a useful quantitative renal biomarker of kidney injury in lupus nephritis and that miR-150, which might be partially induced by TGF-β1, plays an important role in renal fibrosis by increasing profibrotic molecules through downregulation of SOCS1. FFPE kidney specimens (n=25) including baseline and repeated needle renal biopsies were from 14 patients with LN enrolled in IRB-approved protocols at the NIDDK between 1976 and 1999. The specimens were divided in two groups based on histological chronicity index (CI). CI ≥ 4 were categorized as having high degree of chronicity of chronic kidney injury. 18 kidneys from 8 patients including high CI (n=9) and low CI (n=9) were used for miR profiling by Affymetrix microRNA microarrays.

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Lnc453774.1 mediated gene expression in human HK-2 cells

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