Trimetazidine Inhibits Renal Tubular Epithelial Cells to Mesenchymal Transition in Diabetic Rats via Upregulation of Sirt1

Yang, Yong; Wang, Yong; He, Zuowen; Liu, Yunchang; Chen, Chen; Wang, Yan; Wang, Dao Wen; Wang, Hong

doi:10.3389/fphar.2020.01136

Cited by 32 publications

(16 citation statements)

References 77 publications

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“…In DKD, EMT of renal tubular epithelial cells is believed to participate in the progress of tubulointerstitial fibrosis through the accumulation of renal matrix protein. EMT induced by hyperglycemia is generally considered to be the initial factor leading to matrix accumulation and deposition, so EMT is also considered to be an important mechanism of renal fibrosis and renal dysfunction in DKD [ 27 ]. Therefore, targeting EMT is considered a potential therapy to delay the progression of tubulointerstitial fibrosis in DKD [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Berberine protects diabetic nephropathy by suppressing epithelial-to-mesenchymal transition involving the inactivation of the NLRP3 inflammasome

Zhu

Wang

et al. 2022

Renal Failure

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Accumulating evidence has implicated that berberine (BBR) has a beneficial effect on diabetic kidney disease (DKD), but its mechanism is not clear. The aim of this study was to assess whether berberine could alleviate tubulointerstitial fibrosis and attenuate epithelial-to-mesenchymal transition (EMT) and its possible molecular mechanism. High-fat diet (HFD) followed by injection of STZ was used to induce diabetic rats in vivo . After the onset of diabetes, rats were treated with either BBR or saline for 12 weeks. In vitro , the human renal proximal tubular epithelial cell line (HK-2) was exposed to high glucose, with or without BBR. The influence of berberine on renal tubulointerstitial histological changes, markers of epithelial-to-mesenchymal transition (EMT) and (NOD-like receptor pyrin domain-containing protein 3) NLRP3 inflammasome expression were examined. Results showed that in vivo , BBR could significantly ameliorate microalbumin and renal pathologic changes in diabetic rats. Immunofluorescence showed that BBR could inhibit EMT. Furthermore, BBR could down-regulate the level of the NLRP3 inflammasome in diabetic rats. Consistently, in vitro , BBR suppressed high glucose-induced EMT and activation of NLRP3 inflammasome in HK-2. Our study demonstrated that BBR could inhibit high glucose-induced EMT and renal interstitial fibrosis by suppressing the NLRP3 inflammasome. BBR might be used as a novel drug to ameliorate tubulointerstitial fibrosis in DKD.

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Section: Discussionmentioning

confidence: 99%

Berberine protects diabetic nephropathy by suppressing epithelial-to-mesenchymal transition involving the inactivation of the NLRP3 inflammasome

Zhu

Wang

et al. 2022

Renal Failure

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“…The expression of TGF-β 1 mRNA and the TGF-β 1 protein in the kidney tissue of people with diabetes is increased ( Zhang et al, 2017 ). TGF-β 1 is directly involved in the epithelial-to-mesenchymal transition process of DKD, leading to renal interstitial fibrosis ( Zheng et al, 2016 ; Yang Y. et al, 2020 ), and it can activate the downstream Smad signaling pathway, thereby mediating fibrogenesis ( Hathaway et al, 2015 ). The role of TMAO in promoting fibrosis has also been demonstrated in many studies.…”

Section: Discussionmentioning

confidence: 99%

Trimethylamine N-Oxide Exacerbates Renal Inflammation and Fibrosis in Rats With Diabetic Kidney Disease

et al. 2021

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The gut microbiota plays a pivotal role in the onset and development of diabetes and its complications. Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite of certain nutrients, is associated with type 2 diabetes and its complications. Diabetic kidney disease (DKD) is one of the most serious microvascular complications. However, whether TMAO accelerates the development of DKD remains unclear. We tested the hypothesis that TMAO accelerates the development of DKD. A high-fat diet/low-dose streptozotocin-induced diabetes rat model was established, with or without TMAO in the rats’ drinking water. Compared to the normal rats, the DKD rats showed significantly higher plasma TMAO levels at the end of the study. TMAO treatment not only exacerbated the kidney dysfunction of the DKD rats, but also renal fibrosis. Furthermore, TMAO treatment activated the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome and resulted in the release of interleukin (IL)-1β and IL-18 to accelerate renal inflammation. These results suggested that TMAO aggravated renal inflammation and fibrosis in the DKD rats, which provides a new perspective to understand the pathogenesis of DKD and a potential novel target for preventing the progression of DKD.

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“…SIRT1 is a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase that exerts anti-inflammatory and anti-oxidative effects on pathological process in several organs, including kidney 25 , 26 . In the present research, we found that TF inhibited CaOx-induced kidney oxidative stress injury and alleviated kidney crystal deposition by regulating miR-128/SIRT1 axis.…”

Section: Introductionmentioning

confidence: 99%

Theaflavin protects against oxalate calcium-induced kidney oxidative stress injury via upregulation of SIRT1

Ye¹,

Yang²,

Liu³

et al. 2021

Int. J. Biol. Sci.

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Renal tubular cell injury induced by calcium oxalate (CaOx) is a critical initial stage of kidney stone formation. Theaflavin (TF) has been known for its strong antioxidative capacity; however, the effect and molecular mechanism of TF against oxidative stress and injury caused by CaOx crystal exposure in kidneys remains unknown. To explore the potential function of TF on renal crystal deposition and its underlying mechanisms, experiments were conducted using a CaOx nephrocalcinosis mouse model established by glyoxylate intraperitoneal injection, and HK-2 cells were subjected to calcium oxalate monohydrate (COM) crystals, with or without the treatment of TF. We discovered that TF treatment remarkably protected against CaOx-induced kidney oxidative stress injury and reduced crystal deposition. Additionally, miR-128-3p expression was decreased and negatively correlated with SIRT1 level in mouse CaOx nephrocalcinosis model following TF treatment. Moreover, TF suppressed miR-128-3p expression and further abolished its inhibition on SIRT1 to attenuate oxidative stress in vitro. Mechanistically, TF interacted with miR-128-3p and suppressed its expression. In addition, miR-128-3p inhibited SIRT1 expression by directly binding its 3'-untranslated region (UTR). Furthermore, miR-128-3p activation partially reversed the acceerative effect of TF on SIRT1 expression. Taken together, TF exhibits a strong nephroprotective ability to suppress CaOx-induced kidney damage through the recovery of the antioxidant defense system regulated by miR-128-3p/SIRT1 axis. These findings provide novel insights for the prevention and treatment of renal calculus.

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Trimetazidine Inhibits Renal Tubular Epithelial Cells to Mesenchymal Transition in Diabetic Rats via Upregulation of Sirt1

Cited by 32 publications

References 77 publications

Berberine protects diabetic nephropathy by suppressing epithelial-to-mesenchymal transition involving the inactivation of the NLRP3 inflammasome

Berberine protects diabetic nephropathy by suppressing epithelial-to-mesenchymal transition involving the inactivation of the NLRP3 inflammasome

Trimethylamine N-Oxide Exacerbates Renal Inflammation and Fibrosis in Rats With Diabetic Kidney Disease

Theaflavin protects against oxalate calcium-induced kidney oxidative stress injury via upregulation of SIRT1

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