Protective Effect of Znt7 on High Glucose-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells

Zhang, Xiuli; Xu, Li; Liang, Dan; Zhang, Lianzhi; Liu, Shengquan; Yang, Lina; Chen, Zhihong; Gu, Harvest F.

doi:10.1159/000488697

Cited by 23 publications

(27 citation statements)

References 34 publications

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“…Although the presence of some apoptotic tubular cells in both human and experimental DKD is well stablished [60][61][62][63], excessive acute cell death is not a feature of DKD. We do not know the reason of the high cell death values found in vitro, but even higher cell death values have been found in a previous work in which HK-2 cells or NRK-52E renal tubular epithelial cells were exposed to 30 mM glucose/ 1% O 2 and apoptosis was quantified [64]. Furthermore, high glucose or hypoxia separately also induce in cultured proximal tubular cells around 15%-25% apoptotic cell death [65][66][67][68][69][70].…”

Section: Plos Onementioning

confidence: 80%

Time-series proteomic study of the response of HK-2 cells to hyperglycemic, hypoxic diabetic-like milieu

et al. 2020

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During diabetes, renal proximal tubular cells (PTC) are exposed to a combination of high glucose and hypoxic conditions, which plays a relevant role in the development of diabetic kidney disease (DKD). In this work, a time-series proteomic study was performed to analyse the effect of a diabetic-like microenvironment induced changes on HK-2 cells, a human cell line derived from normal proximal tubular epithelial cells. Cells simultaneously exposed to high glucose (25 mM) and hypoxia (1% O 2) were compared to cells in control conditions for up to 48 h. Diabetic conditions increased the percentage of death cells after 24 and 48 h, but no differences in the protein/cell ratio were found. The relative protein quantification using dimethyl-labeling and UHPLC-MS/MS analysis allowed the identification of 317, 296 and 259 proteins at 5, 24 and 48 h, respectively. The combination of statistical and time expression profile analyses indicated an increased expression of proteins involved in glycolysis, and a decrease of cytoskeletal-related proteins. The exposure of HK-2 cells to high glucose and hypoxia reproduces some of the effects of diabetes on PTC and, with the limitations inherent to in vitro studies, propose new mechanisms and targets to be considered in the management of DKD.

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Section: Plos Onementioning

confidence: 80%

Time-series proteomic study of the response of HK-2 cells to hyperglycemic, hypoxic diabetic-like milieu

et al. 2020

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“…The MAPK signaling pathway plays a role in EMT of the various kinds of epithelial cells and includes JNK, p38 MAPK, and ERK (Yang, Lee, & Shin, ; Zhang, Lian, & Liang, ; Zhang, Wang, & Fan, ). In order to assess the effect of mulberry leaves extracts on high glucose‐stimulated ERK1/2 activation, the expressions of phospho‐ERK1/2 were detected by western blot.…”

Section: Resultsmentioning

confidence: 99%

The mechanism of mulberry leaves against renal tubular interstitial fibrosis through ERK1/2 signaling pathway was predicted by network pharmacology and validated in human tubular epithelial cells

Zhu

et al. 2019

Phytotherapy Research

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Mulberry leaf was reported that it has antidiabetic activity, although the mechanisms underlying the function have not been fully elucidated. In the present study, the results of network pharmacology suggested that mulberry leaves could regulate key biological process in development of diabetes, and the process implicates multiple signaling pathways, such as JAK-STAT, MAPK, VEGF, PPAR, and Wnt. Then, the research in vitro indicated that mulberry leaves remarkably ameliorated high glucose-induced epithelial to mesenchymal transition, which was characterized with significant reduction of intracellular reactive oxygen species (ROS) levels as well as downregulation of NADPH oxidase subunits NOX1, NOX2, and NOX4, and it was found to be connected with the ERK1/2 signaling pathway in human tubular epithelial cells (HK-2). Moreover, the results of bioinformatics and the dual luciferase report showed that ZEB1 might be a target gene of miR-302a; decreased miR-302a and increased ZEB1 expressions could significantly promote epithelial to mesenchymal transition. However, mulberry leaves could reverse these modulations. Our results demonstrated that network pharmacology could provide a guidance role for traditional Chinese medicine research, and mulberry leaves could be of benefit in preventing high glucose-induced EMT in HK-2 cells, which proved that it was related to the upregulation of miR-302a by targeting ZEB1 and the inhibition of NADPH oxidase/ROS/ERK1/2 pathway.

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“…Astilbin [140], astragaloside IV [15], curcumin [41], Psoralea corylifolia [115], quercetin [49], secoisolariciresinol diglucoside [88], silybin [43], berberine [45], berberine [44], berberine [136], tripterygium glycosides [138], celastrol [170], curcumin [132], resveratrol [133], astragaloside IV [103], Cyclocarya paliurus-triterpenic acids-enriched fraction [142], ferulic acid [145]…”

Section: Apoptosismentioning

confidence: 99%

Mechanisms of Herbal Nephroprotection in diabetes mellitus

Dragoș

Manea

Timofte

et al. 2020

Journal of Diabetes Research

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Diabetic nephropathy (DN) is a leading cause of kidney morbidity. Despite the multilayered complexity of the mechanisms involved in the pathogenesis of DN, the conventional treatment is limited to just a few drug classes fraught with the risk of adverse events, including the progression of renal dysfunction. Phytoceuticals offer a promising alternative as they act on the many-sidedness of DN pathophysiology, multitargeting its intricacies. This paper offers a review of the mechanisms underlying the protective action of these phytoagents, including boosting the antioxidant capabilities, suppression of inflammation, averting the proliferative and sclerosing/fibrosing events. The pathogenesis of DN is viewed as a continuum going from the original offense, high glucose, through the noxious products it generates (advanced glycation end-products, products of oxidative and nitrosative stress) and the signaling chains consequently brought into action, to the harmful mediators of inflammation, sclerosis, and proliferation that eventually lead to DN, despite the countervailing attempts of the protective mechanisms. Special attention was given to the various pathways involved, pointing out the ability of the phytoagents to hinder the deleterious ones (especially those leading to, driven by, or associated with TGF-β activation, SREBP, Smad, MAPK, PKC, NF-κB, NLRP3 inflammasome, and caspase), to promote the protective ones (PPAR-α, PPAR-γ, EP4/Gs/AC/cAMP, Nrf2, AMPK, and SIRT1), and to favorably modulate those with potentially dual effect (PI3K/Akt). Many phytomedicines have emerged as potentially useful out of in vitro and in vivo studies, but the scarcity of human trials seriously undermines their usage in the current clinical practice—an issue that stringently needs to be addressed.

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Protective Effect of Znt7 on High Glucose-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells

Cited by 23 publications

References 34 publications

Time-series proteomic study of the response of HK-2 cells to hyperglycemic, hypoxic diabetic-like milieu

Time-series proteomic study of the response of HK-2 cells to hyperglycemic, hypoxic diabetic-like milieu

The mechanism of mulberry leaves against renal tubular interstitial fibrosis through ERK1/2 signaling pathway was predicted by network pharmacology and validated in human tubular epithelial cells

Mechanisms of Herbal Nephroprotection in diabetes mellitus

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