LncRNA-ATB participates in the regulation of calcium oxalate crystal-induced renal injury by sponging the miR-200 family

Molecular Medicine

Jihang Yuan¹  Haiyan Hu²  Tingting Zhao²  Chao Zhu²  Jiarong Ding²  Tao Ding²  Zhiyong Guo²  Yinhui Li² 

[1] Department of Medical Genetics, The Naval Military Medical University, 200433, Shanghai, People’s Republic of China;Department of Nephrology, The First Affiliated Hospital of Naval Military Medical University, 200433, Shanghai, People’s Republic of China;

关键词: lncRNA-ATB;    EMT;    miR-200a;    Calcium oxalate monohydrate;    Kidney stone;    Calcium oxalate;   

DOI  :  10.1186/s10020-021-00403-2

来源: Springer

【 摘 要 】

BackgroundLncRNA-ATB is a long noncoding RNA (lncRNA) activated by transforming growth factor β (TGF-β) and it has important biological functions in tumours and nontumour diseases. Meanwhile, TGF-β is the most critical regulatory factor in the process of nephrotic fibrosis and calcium oxalate (CaOx) crystal-induced renal injury. The present study aimed to investigate the biological function and mechanism of lncRNA-ATB in CaOx crystal-induced renal injury.MethodsThe expression level of lncRNA-ATB was detected by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), the expression levels of epithelial-mesenchymal transition (EMT) markers, TGF-β1 and Kidney Injury Molecule-1 (KIM-1) were detected by qRT-PCR, immunofluorescence staining or western blot analysis, cell proliferation was measured with a CCK-8 kit, cell apoptosis was measured by flow cytometry and TUNEL staining, and cell injury was detected with the Cytotoxicity lactate dehydrogenase (LDH) Assay kit and the expression level of KIM-1.ResultsThe expression levels of lncRNA-ATB and TGF-β1 were significantly increased in HK-2 cells after coincubation with calcium oxalate monohydrate (COM). COM stimulation caused significant injury in the HK-2 cells, induced cell apoptosis, inhibited cell proliferation, and induced EMT changes. After COM stimulation, the expression levels of the epithelial cell markers E-cadherin and zonula occludens (ZO)-1 in HK-2 cells significantly decreased, whereas the levels of the mesenchymal cell markers N-cadherin, vimentin and α-smooth muscle actin (α-SMA) significantly increased. Interference with lncRNA-ATB expression significantly relieved the COM-induced cell injury, cell apoptosis, proliferation inhibition, and EMT changes. The expression levels of the microRNA-200 (miR-200) family in the HK-2 cells after coincubation with COM were significantly decreased. MiR-200a mimics relieved the COM-induced cell injury, apoptosis, proliferation inhibition, and EMT changes, whereas miR-200a inhibitors abolished the lncRNA-ATB interference-induced relief of the COM-induced cell injury, apoptosis, proliferation inhibition, and EMT.ConclusionLncRNA-ATB promoted the COM-induced cell injury, cell apoptosis, proliferation inhibition, and EMT to participate in the process of CaOx crystal-induced renal injury by sponging miR-200s.

【 授权许可】

CC BY