scholarly journals ErHuang Formula Improves Renal Fibrosis in Diabetic Nephropathy Rats by Inhibiting CXCL6/JAK/STAT3 Signaling Pathway

2020 ◽  
Vol 10 ◽  
Author(s):  
Yu-Li Shen ◽  
Yi-ping Jiang ◽  
Xiao-Qin Li ◽  
Su-Juan Wang ◽  
Ming-Hua Ma ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Renal Fibrosis ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

scholarly journals Renoprotective Effect of the Recombinant Anti-IL-6R Fusion Proteins by Inhibiting JAK2/STAT3 Signaling Pathway in Diabetic Nephropathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Nanwen Zhang ◽  
Qingmei Zheng ◽  
Yaduan Wang ◽  
Juan Lin ◽  
He Wang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Interleukin 6 ◽  
Fusion Proteins ◽  
Mesangial Cells ◽  
Glomerular Mesangial Cells ◽  
Stat3 Pathway ◽  
Renoprotective Effect ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

Diabetic nephropathy the main reason for end stage renal disease is a common microvascular complication in patients with type 1 and type 2 diabetes. The interleukin-6 (IL-6), acting as a pleiotropic cytokine, play key roles in main autoimmune disorders. The recombinant anti-IL-6R fusion proteins (VHH-0031) constructed and obtained in our lab is a dual target-directed single domain-based fusion protein against the interleukin-6 receptor. This study aims to explore the renoprotective effect of VHH-0031 in diabetic nephropathy. VHH-0031 treatment alleviated renal inflammation, morphologic injury and renal insufficiency in both Goto-Kakizaki rats and STZ-induced Sprague Dawley rats. These renoprotective effects of VHH-0031 are associated with alleviating inflammation and suppression of the JAK2/STAT3 signaling pathway. The mesangial cells treated with VHH-0031 exhibited anti-proliferation, anti-inflammation and inactivation of JAK2/STAT3 pathway under high glucose condition. In conclusion, this study demonstrates that VHH-0031 exhibited a potent protective effect in kidney of diabetic rats and its mechanism may be concerned with the inhibition of the IL-6R/JAK2/STAT3 pathway of glomerular mesangial cells.

scholarly journals lncRNA MALAT1 Promotes Renal Fibrosis in Diabetic Nephropathy by Targeting the miR-2355-3p/IL6ST Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Haozi Huang ◽  
Guowei Zhang ◽  
Zhenying Ge
Keyword(s):  
Diabetic Nephropathy ◽  
Renal Fibrosis ◽  
Cell Damage ◽  
Diabetic Rats ◽  
Luciferase Reporter ◽  
Signal Transducer ◽  
Luciferase Reporter Gene ◽  
Protein Levels ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

Long noncoding RNA (lncRNAs) metastasis–associated lung adenocarcinoma transcript 1 (MALAT1) has been reported in diabetic nephropathy (DN) about its effect on podocyte function and cell heat shock induced by hyperglycemia. However, the biological mechanism of MALAT1 regulating DN fibrosis needs further study. In this study, SD rats were administrated with streptozotocin (STZ) to establish a diabetes model. In vitro, human renal tubular epithelial cells (HK-2 and 293T) were treated with high glucose (HG). Here, we found that MALAT1 was upregulated in renal tissues of diabetic rats and HG-treated cells, and HG treatment promoted cell proliferation and invasion. MALAT1 overexpression aggravated protein levels of collagen I (col I), collagen IV (col IV), fibronectin (FN), and laminin (LN) in HK-2 cells, while MALAT1 knockdown exerted the opposite effect. Moreover, the luciferase reporter gene and pull-down assays demonstrated that MALAT1 interacted with miR-2355-3p. The miR-2355-3p level was downregulated in diabetic rats and HG-treated cells, and MALAT1 overexpression inhibited the miR-2355-3p level. Bioinformatics prediction and luciferase reporter gene assay revealed that interleukin 6 signal transducer (IL6ST) was a target of miR-2355-3p. In addition, miR-2355-3p overexpression attenuated fibrosis-related gene levels in HG-treated cells by inhibiting IL6ST expression and inactivating the recombinant signal transducer and activator of the transcription 3 (STAT3) signaling pathway. Knockdown of miR-2355-3p reversed the inhibitory effect of MALAT1 knockdown on IL6ST, col I, col IV, FN, and LN protein levels in HG-induced cells. Overexpression of MALAT1 aggravated cell damage in HG-induced cells via the miR-2355-3p/IL6ST/STAT3 signaling pathway. Finally, enhanced renal fibrosis and kidney tissue damage were observed in diabetic rats. In conclusion, MALAT1 overexpression may enhance renal fibrosis in diabetic rats and cell damage in HG-induced HK-2 cells via the miR-2355-3p/IL6ST axis, which provides a new perspective of DN treatment.

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