Tanshinone IIA attenuates high glucose-induced epithelial-to-mesenchymal transition in HK-2 cells through VDR/Wnt/β-catenin signaling pathway

Zeng, Jing-Yi; Bao, Xiaoyong

doi:10.5603/fhc.a2021.0025

Cited by 11 publications

(11 citation statements)

References 37 publications

(38 reference statements)

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“…Recently, STAT5 was reported to play a crucial role in the susceptibility to diabetes pathologies, 10 and participated in modulation of epithelial‐to‐mesenchymal transition 11 . And high glucose treatment could mediate epithelial‐mesenchymal transition in tubulointerstitial and proximal tubular cells 21,22 . This work indicated that high glucose/hyperglycemia increased STAT5A levels in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 79%

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STAT5A modulated EndMT via upregulation of ELTD1 expression in diabetic nephropathy

Tian

et al. 2022

Clin Exp Pharma Physio

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Diabetic nephropathy (DN), one of microvascular complications of diabetes mellitus, results in renal dysfunction and end-stage renal disease. Recently, endothelial-tomesenchymal transition (EndMT) was reported to mediate glomerular endothelial dysfunction, therefore, participating in the progress of fibrosis in DN. As a special type of epithelial-to-mesenchymal transition, EndMT and epithelial-to-mesenchymal transition may share corporate modulators. It was reported that epidermal growth factor (EGF), latrophilin and seven transmembrane domain containing 1 (ELTD1) and signal transducer and activator of transcription 5A (STAT5A) participate in epithelialto-mesenchymal transition in some situations. In this work, we proposed that STAT5A participated in high glucose-mediated EndMT via modulation of ELTD1 levels in DN. Our data indicated that hyperglycemia/high glucose-induced ELTD1 and EndMT in DN rats and hyperglycemic human glomerular endothelial cells (HGECs). Additionally, high glucose mediated STAT5A nuclear translocation in HGECs. High glucose-mediated EndMT was reversed by ELTD1 silencing. Moreover, STAT5A was found to be elevated in DN rats and hyperglycemic HGECs. The effect of high glucose-mediated increase of ELTD1 expression and EndMT was reversed by STAT5A silencing in vitro. Further, STAT5A overexpression enhanced ELTD1 levels and EndMT, which was inhibited by si-ELTD1. Chromatin immunoprecipitation (ChIP) and luciferase assay represented that STAT5A directly regulated ELTD1 transcription.Signal transducer and activator of transcription 5A directly regulated ELTD1 transcription, therefore, participating in high glucose-mediated EndMT in glomeruli of DN.

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Section: Discussionmentioning

confidence: 79%

“…11 And high glucose treatment could mediate epithelial-mesenchymal transition in tubulointerstitial and proximal tubular cells. 21,22 This work has some limitations, which may be future directions.…”

Section: Discussionmentioning

confidence: 99%

STAT5A modulated EndMT via upregulation of ELTD1 expression in diabetic nephropathy

Tian

et al. 2022

Clin Exp Pharma Physio

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“…α-SMA is a specific marker of interstitial cells, which is expressed at a low level in normal tissues and organs but upregulated in tissues or cells during interstitial transdifferentiation. Studies have shown that the level of α-SMApositive expression is positively correlated with the degree of tissue fibrosis, and a large amount of α-SMA expression is a marker of epithelial and mesenchymal cell transformation [27].…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Rhein on Renal Interstitial Fibrosis via the SHH-Gli1 Signal Pathway

Luo

Jiang

Cheng

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Rhein is the main extract of Rheum palmatum L., which has been proved to improve the renal function of chronic kidney disease, but its mechanism is not clear. Therefore, this experiment explored the potential pharmacological effect of rhein on renal interstitial fibrosis rats. Methods. This study explores the potential pharmacological action of rhein. In this work, we investigate the potential pharmacological action of rhein in unilateral urethral obstruction (UUO) rats. Thirty Sprague Dawley rats were randomly divided into three groups: sham, UUO, and rhein (rhein-treated UUO rats) groups. The left ureters of the UUO group rats were exposed and bluntly dissected. The rhein group rats were administered an intragastric gavage of rhein (2 mg·kg−1·d−1) for 14 d. Kidney function-related indicators were monitored in these rats, while indexes of pathologic aspects were determined histologically. The expression of α-SMA, TGF-β1, SHH, Gli1, and Snail was quantified using real-time polymerase chain reaction and western blotting. The NRK-49F cells were incubated with and without SHH (100 ng·ml−1) for 48 hours. The SHH-activated NRK-49F cells were incubated with cyclopamine (CNP, 20 umol L−1) or rhein (1 ng·ml−1). The Gli1 and Snail mRNA and protein level were detected. Results. In the in vivo experiment, the results exhibited that UUO caused renal pathological damages. However, these changes could be significantly reversed by the administration of rhein. Compared with the untreated UUO group, the rhein group showed reduced kidney tubular atrophy and necrosis, interstitial fibrosis, hyperplasia, and abnormal deposition of extracellular matrix. Rhein reduced the RNA and protein expression of SHH, Gli1, and Snail of the UUO rats. In the in vitro experiment, CNP or rhein treatment decreased the expression of Gli1 and Snail on mRNA and protein levels in SHH-induced NRK-49F cells, suggesting that CNP or rhein suppresses SHH-induced NRK-49F activation. Taken together, these results demonstrated that rhein suppresses SHH-Gli1-Snail signal pathway activation, with potential implications for the treatment of renal fibrosis. Conclusions. Treatment with rhein remarkably ameliorated renal interstitial fibrosis in UUO rats by regulating the SHH-Gli1-Snail signal pathway.

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“…Tanshinone IIA was demonstrated to have excellent anti-fibrotic properties in streptozotocin-induced and 5/6 nephrectomy models, respectively ( Ahn et al, 2010 ; Xu et al, 2020 ). More importantly, the mechanism for SM against renal fibrosis might be related to reducing endoplasmic reticulum stress to attenuate PERK signaling activities, decreasing expressions of Ang II, TGF-β1 and collagen IV, attenuating high glucose-induced EMT by up-regulating VDR levels on Wnt/β-catenin pathway and inhibiting HG-induced the epithelial-myofibroblast trans differentiation pathway ( Ahn et al, 2010 ; Cao et al, 2017 ; Xu et al, 2020 ; Zeng and Bao, 2021a ).…”

Section: Pharmacological Actions Of Salvia Miltiorrhiza ...mentioning

confidence: 99%

Salvia miltiorrhiza in thorax and abdomainal organ fibrosis: A review of its pharmacology

Zhao

Ping

et al. 2022

Front. Pharmacol.

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Organ fibrosis is a common pathological change that finally results in organ failure, which involves the destruction of parenchyma cells, the activation of mesenchymal cells and the imbalance of immunological cells. In recent years, although some breakthroughs have been made in understanding the pathogenesis and therapeutics of organ fibrosis, no registered drugs could directly target the fibrotic process, which constitutes a major biomedical challenge. Salvia miltiorrhiza (SM) is a well-known medicinal plant in China, which has been widely applied because of its pharmacological effects on anti-oxidative, anti-myocardial infarction, anti-fibrotic, anti-inflammatory, and anti-neoplastic properties. Accumulated evidence suggested that SM played critical roles against organ fibrosis in vivo and in vitro experiments by its multiple biological compounds. In this review, we discussed the recent advances on the phytochemistry and pharmacological mechanisms of SM and its active ingredients in liver, lung, kidney, and heart fibrosis, which might help to promote the treatment of fibrotic diseases in thorax and abdomainal viscera in clinic.

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Tanshinone IIA attenuates high glucose-induced epithelial-to-mesenchymal transition in HK-2 cells through VDR/Wnt/β-catenin signaling pathway

Abstract: This article has been peer reviewed and published immediately upon acceptance.It is an open access article, which means that it can be downloaded, printed, and distributed freely, provided the work is properly cited. Articles in "Folia Histochemica et Cytobiologica" are listed in PubMed.

Cited by 11 publications

References 37 publications

STAT5A modulated EndMT via upregulation of ELTD1 expression in diabetic nephropathy

STAT5A modulated EndMT via upregulation of ELTD1 expression in diabetic nephropathy

Inhibitory Effects of Rhein on Renal Interstitial Fibrosis via the SHH-Gli1 Signal Pathway

Salvia miltiorrhiza in thorax and abdomainal organ fibrosis: A review of its pharmacology

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