Tanshinone IIA improves diabetes‐induced renal fibrosis by regulating the miR‐34‐5p/Notch1 axis

Abstract

The purpose of this study was to evaluate the improvement of tanshinone in renal fibrosis in vitro and in vivo study. It used streptozotocin to model diabetic nephropathy (DN) mice, and treated with different Tanshinone IIA concentrations. The pathology of kidney tissues was evaluated by hematoxylin and eosin (H&E) and Masson's staining; the ultrastructure and apoptosis cell number of kidney tissues were evaluated by transmission electron microscopy (TEM) and TUNEL assay. Relative gene and protein expression was evaluated by reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR), immunohistochemical (IHC) analysis, or western blot (WB) assay. In vitro study, using high‐glucose stimulated HK‐2 cell to model DN cell model, measuring cell proliferation, apoptosis rate, relative gene and protein expression, and LC 3B and P62 proteins expression by Cell Counting Kit‐8 (CCK‐8), flow cytometry, RT‐qPCR, WB, and cell immunofluorescence. Analysis correlation between Notch1 and miRNA‐34a‐5p was carried out by dual‐luciferase reporter. Fibrosis area and apoptosis cell rate were significantly up‐regulated (p < .001), with Tanshinone IIA supplement. The fibrosis area and apoptosis cell rate were also significantly improved in a dose‐dependent manner (p < .05). With si‐miRNA‐34a‐5p transfection, the Tanshinone IIA's treatment effects were significantly depressed. By dual‐luciferase reporter, miRNA‐34a‐5p could target Notch1 in the HK‐2 cell line. Tanshinone IIA improved DN‐induced renal fibrosis by regulating miRNA‐34a‐5p in vitro and in vivo study.

Selection of Ideal Reference Genes for Gene Expression Analysis in COVID-19 and Mucormycosis

“…NRF2 is a master regulator for an array of antioxidant responses, and excessive oxidative stress is a well-documented hallmark of COVID-19 pathophysiology ( 34 ). However, in SARS-CoV-2 infection, NRF2 expression is dysregulated and not sufficiently induced to mount an effective antioxidant response ( 35 ). The relative suppression of NRF2 expression is a viral strategy to hijack host protective responses ( 35 ), and pharmacological induction of NRF2 expression is proposed to be an effective strategy against COVID-19 ( 36 ).…”

“…NRF2 is a major redox regulator that is significantly induced in response to oxidative stress. Nonetheless, as a component of viral strategy to hijack host protective responses, NRF2 expression is dysregulated during COVID-19, is not sufficiently upregulated, and remains relatively suppressed/minimally induced to mount an effective antioxidant response ( 30 , 35 ). Based on normalization with CypA , we obtained a relatively stable NRF2 induction profile in mild (<2-fold), asymptomatic (<3-fold), moderate (<5-fold), pre-CAM (<13-fold), and post-CAM (<3-fold) groups.…”

Clinical efficacy and safety of Xuefu Zhuyu decoction in the treatment of diabetic kidney disease: A protocol for systematic review and meta-analysis

“…However, Traditional Chinese medicine has a significant effect on the treatment of chronic kidney disease, and some experts suggest that using triptolide and emodin can improve the treatment of proteinuria in the treatment of chronic kidney disease, [16,17] traditional Chinese medicine ingredients such as ginsenosides, tanshinone IIA, anthocyanin also have beneficial effects on DKD. [18][19][20] Xuefu Zhuyu decoction, as the first prescription of promoting blood circulation and removing blood stasis, it has more clinical RCTs for DKD, especially in China. However, there is no systematic review comprehensively describing the effectiveness and safety of Xuefu Zhuyu decoction for DKD.…”

Renoprotective Effects of Tanshinone IIA: A Literature Review

“…Zeng et al [ 39 ] used HG-stimulated HK-2 cells in vitro, and the study showed that Tan IIA was able to increase E-cadherin in cells by increasing vitamin D receptor (VDR) protein levels and inhibiting β-catenin and glycogen synthetase kinase-3β (GSK-3β) protein levels and decreased a-SMA expression, thereby attenuating EMT, suggesting that Tan IIA may inhibit the Wnt/β-catenin pathway by upregulating VDR, and thus attenuates high glucose-induced EMT in HK-2 cells. Zhang et al [ 40 ] found that Tan IIA may promote autophagy in the renal tissues of DN rats and HK-2 cells induced by high glucose by regulating the miR-34-5p/Notch1 axis, thereby improving renal tubular fibrosis induced by DN. Wang et al [ 41 ] found that Tan IIA reduced urinary protein excretion and serum creatinine (SCR) levels and attenuated glomerulosclerosis and renal inflammation in CKD rats.…”