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      LncRNA CASC2 Alleviates the Progression of Diabetic Nephropathy by Regulating the miR-144/SOCS2 Signalling Axis

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          Background: Diabetic nephropathy constitutes a large proportion of end-stage kidney failure in diabetic patients. However, the underlying molecular mechanisms remain unclear. Methods: Db/db diabetic mouse models and high glucose (HG)-induced human renal mesangial cells (HRMCs) were used as research models in vivo and in vitro. The expression of cancer susceptibility candidate 2 (CASC2) was quantified by qRT-PCR. The regulatory role of CASC2 in cell apoptosis, inflammatory factor release, and fibrosis was verified by flow cytometry, qRT-PCR, and Western blot assay, respectively. The bioinformatics prediction software DIANA and starBase v2.0 were used to predict the putative binding sites. The interactions among CASC2, miR-144, and SOCS2 were explored by the luciferase assay and Western bolt assay. Results: The expression of CASC2 in diabetic mouse models and HG-induced HRMCs was lower than that in the control ( p < 0.05). Overexpression of CASC2 resulted in a decrease in the apoptosis rate, inflammatory factor release (TNF-α, IL-6, and IL-1β), expression of cleaved caspase-3, and fibrotic proteins (fibronectin, Col-IV, and TGF-β1) and an increase in Bcl-2 expression. Inhibition of CASC2 caused increased expression of miR-144. Furthermore, mechanistic investigations confirmed that activation of the miR-144/SOCS2 regulatory loop by overexpression of miR‐144 reversed the in vitro effects of CASC2 on inhibiting cell apoptosis, inflammatory factor release, and fibrosis. In addition, simultaneous overexpression of miR-144 and SOCS2 further increased the inhibition of cell apoptosis, inflammatory factor release, and fibrosis by CASC2. Conclusion: CASC2 could alleviate the degree and process of apoptosis, inflammation, and fibrosis in diabetic nephropathic models by regulating the miR-144/SOCS2 axis.

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          Most cited references 41

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              Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus

               J. Liu,  J J A Yao,  X. M. Li (2014)
              Long noncoding RNAs (lncRNAs) have important roles in diverse biological processes. Our previous study has revealed that lncRNA-MALAT1 deregulation is implicated in the pathogenesis of diabetes-related microvascular disease, diabetic retinopathy (DR). However, the role of MALAT1 in retinal vasculature remodeling still remains elusive. Here we show that MALAT1 expression is significantly upregulated in the retinas of STZ-induced diabetic rats and db/db mice. MALAT1 knockdown could obviously ameliorate DR in vivo, as shown by pericyte loss, capillary degeneration, microvascular leakage, and retinal inflammation. Moreover, MALAT1 knockdown could regulate retinal endothelial cell proliferation, migration, and tube formation in vitro. The crosstalk between MALAT1 and p38 MAPK signaling pathway is involved in the regulation of endothelial cell function. MALAT1 upregulation represents a critical pathogenic mechanism for diabetes-induced microvascular dysfunction. Inhibition of MALAT1 may serve as a potential target for anti-angiogenic therapy for diabetes-related microvascular complications.

                Author and article information

                Kidney Blood Press Res
                Kidney and Blood Pressure Research
                S. Karger AG
                December 2020
                23 November 2020
                : 45
                : 6
                : 837-849
                aThe First Affiliated Hospital of Soochow University, Suzhou, China
                bDepartment of Nephrology, People’s Hospital of XueCheng, Zaozhuang, China
                Author notes
                *Yan Xie, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006 (China),
                508078 Kidney Blood Press Res 2020;45:837–849
                © 2020 The Author(s). Published by S. Karger AG, Basel

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                Page count
                Figures: 6, Tables: 1, Pages: 13
                Research Article


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