Transcriptome Identified lncRNAs Associated with Renal Fibrosis in UUO Rat Model

Abstract

Renal fibrosis represents a final common outcome of many renal diseases and has attracted a great deal of attention. To better understand whether lncRNAs could be a player in this process or be a biomarker for renal fibrosis diagnosis, we compared transcriptome sequencing data on renal tissues and urine respectively between UUO (unilateral ureteral obstruction) and shamed (Sham) rat model. Numerous genes including lncRNAs with significant changes in their expression were identified. 24 lncRNAs were up-regulated and 79 lncRNAs were down-regulated in the renal tissues of the UUO rats. 625 lncRNAs were up-regulated and 177 lncRNAs were down-regulated in urines of the UUO rats. Among the lncRNAs upregulated in renal tissue of UUO rats, 19 lncRNAs were predicted containing several conserved Smad3 binding motifs in the promoter. Among them, lncRNAs with putative promoter containing more than 4 conserved Smad3 binding motifs were demonstrated to be induced by TGF-β significantly in normal rat renal tubular epithelial NRK-52E cells. We further confirmed that lncRNA TCONS_00088786 and TCONS_01496394 were regulated by TGF-β stimulation and also can influence the expression of some fibrosis-related genes through a feedback loop. Based on transcriptome sequencing data, bioinformatics analysis and qRT-PCR detection, we also demonstrated lncRNA in urine are detectable and might be a novel biomarker of renal fibrosis. These results provide new information for the involvement of lncRNAs in renal fibrosis, indicating that they may serve as candidate biomarkers or therapeutic targets in the future.

Diverse Role of TGF-β in Kidney Disease

“…In addition, several TGF-β/Smad3-associated lncRNAs are found to be associated with renal fibrosis. TCONS_00088786 and TCONS_01496394 are TGF-β/Smad3-associated lncRNAs as they contain potential binding sites for Smad3 and silencing TCONS_00088786 inhibits renal interstitial fibrosis by targeting miR-132 (Sun et al, 2017;Zhou S.G. et al, 2018). lncRNA-ATB is highly upregulated in patients with acute renal allograft rejection and renal carcinoma and is able to promote EMT (Qi et al, 2017;Qiu et al, 2017;Zhou and Jiang, 2019).…”

miR‐185 affected the EMT, cell viability, and proliferation via DNMT1/MEG3 pathway in TGF‐β1‐induced renal fibrosis

“…In recent decades, researches documented that lncRNAs were involved in variety of human diseases, such as respiratory system-related diseases, immune system-related diseases, nervous systemrelated diseases, endocrine related diseases, cardiovascular disease, urogenital system-related diseases, and variety of cancers (Wapinski and Chang, 2011;Batista and Chang, 2013;Latronico and Condorelli, 2015;Haemmig et al, 2017;Rogoyski et al, 2017). Reports demonstrated that several lncRNAs were involved in the TGF-β-induced renal fibrosis, including lncRNA H19, lncRNA ENSMUST00000147869, lincRNA-Gm4419, lncRNA Erbb4-IR, and so on (Jiang and Zhang, 2017;Sun et al, 2017). Sun et al (2018) demonstrated that Erbb4-IR promoted the renal fibrosis by inhibiting the miR-29b expression.…”

Serum lncRNA HAND2-AS1 is downregulated in diabetic patients with chronic renal failure and ameliorates cell apoptosis

“…These lncRNAs show upregulated or downregulated expression pattern to promote or inhibit the development of diabetic complications. Onset of chronic renal failure also globally affects the expression of genes including lncRNAs, while the specific functionality of lncRNAs in this disease has rarely been studied [14]. In this study, we observed downregulated expression of lncRNA HAND2-AS1 in diabetic patients with chronic renal failure but not in diabetic patients without obvious complications.…”