Resveratrol reduces gentamicin-induced EMT in the kidney via inhibition of reactive oxygen species and involving TGF-β/Smad pathway

Beshay, Olivia N; Ewees, Mohamed G.; Abdel-Bakky, Mohamed Sadek; Hafez, Sara Mohamed Naguib Abdel; Abdelrehim, Amany B.; Bayoumi, Asmaa M.A.

doi:10.1016/j.lfs.2020.118178

Cited by 44 publications

(28 citation statements)

References 55 publications

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“…To determine the mechanical link between NETs and EMT in pancreatic cancer cells, we investigated several important EMT relative pathways such as EGFR, 31 WNT, 32 TGF‐β, 33 AKT 34 and mTOR 35 pathway.…”

Section: Resultsmentioning

confidence: 99%

Neutrophil extracellular DNA traps promote pancreatic cancer cells migration and invasion by activating EGFR/ERK pathway

Jin

Yin

et al. 2021

J Cellular Molecular Medi

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Neutrophil extracellular DNA traps (NETs) are newly discovered forms of activated neutrophils. Increasing researches have shown that NETs play important roles in cancer progression. Our previous study has proved that tumour‐infiltrating NETs could predict postsurgical survival in patients with pancreatic ductal adenocarcinoma (PDAC). However, the roles of NETs on the progression of pancreatic cancer are unknown. Here, we investigated the effects of NETs on pancreatic cancer cells. Results showed that both PDAC patients’ and normal individuals’ neutrophils‐derived NETs could promote migration and invasion of pancreatic cancer cells with epithelial‐mesenchymal transition. Further, study confirmed that EGFR/ERK pathway played an important role in this progression. The addition of neutralizing antibodies for IL‐1β could effectively block the activation of EGFR/ERK companied with reduction of EMT, migration and invasion. Taken together, NETs facilitated EMT, migration and invasion via IL‐1β/EGFR/ERK pathway in pancreatic cancer cells. Our study suggests that NETs may provide promising therapeutic targets for pancreatic cancer.

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Section: Resultsmentioning

confidence: 99%

Neutrophil extracellular DNA traps promote pancreatic cancer cells migration and invasion by activating EGFR/ERK pathway

Jin

Yin

et al. 2021

J Cellular Molecular Medi

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“…These results were in compliance with previous studies indicating the renoprotective effects of D-lim [ 30 , 54 ]. It has also been reported that other natural compounds with antioxidant activity such as gossypin [ 55 ], resveratrol [ 56 ], and ferulic acid [ 57 ] ameliorated renal histopathological changes and altered renal function after GM injection. Therefore, D-lim may increase GFR following the improvement of renal histopathological changes and finally reduce serum levels of urea and Cr.…”

Section: Discussionmentioning

confidence: 99%

D‐Limonene Alleviates Acute Kidney Injury Following Gentamicin Administration in Rats: Role of NF‐κB Pathway, Mitochondrial Apoptosis, Oxidative Stress, and PCNA

Babaeenezhad

Moradi

Monfared

et al. 2021

Oxidative Medicine and Cellular Longevity

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Clinical application of gentamicin (GM) is well known to be associated with the development of acute kidney injury (AKI). This study was the first to investigate the possible protective effects of D-limonene (D-lim) on AKI following GM administration in rats. 32 rats arranged in four groups ( n = 8 ): (1) the control group received saline intraperitoneally (0.5 ml/day) and orally (0.5 ml/day), (2) the D-lim group received D-lim (100 mg/kg) orally and saline (0.5 ml/day) intraperitoneally, (3) the GM group received GM (100 mg/kg/day) intraperitoneally and saline (0.5 ml/day) orally, and (4) the treated group received intraperitoneal GM (100 mg/kg) and oral D-lim (100 mg/kg). All treatments were performed daily for 12 consecutive days. Results revealed that D-lim ameliorated GM-induced AKI, oxidative stress, mitochondrial apoptosis, and inflammation. D-lim showed nephroprotective effects as reflected by the decrease in serum urea and creatinine and improvement of renal histopathological changes. D-lim alleviated GM-induced oxidative stress by increasing the activities of renal catalase, serum and renal glutathione peroxidase, and renal superoxide dismutase and decreasing renal malondialdehyde and serum nitric oxide levels. Intriguingly, D-lim suppressed mitochondrial apoptosis by considerably downregulating Bax and caspase-3 (Casp-3) mRNA and protein expressions and markedly enhancing Bcl2 mRNA and protein expressions. Furthermore, D-lim significantly decreases GM-induced inflammatory response through downregulation of NF-κB, IL-6, and TNF-α mRNA and/or protein expressions and decrease in renal myeloperoxidase activity. Finally, D-lim remarkably downregulated PCNA protein expression in the treated group compared with the GM group. In brief, this study showed that D-lim alleviated AKI following GM administration in rats, partially through its antioxidant, anti-inflammatory, and antiapoptotic activities as well as downregulation of PCNA expression.

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“…Since EMT activation results in a vicious cycle of renal fibrosis that in turn induces more severe renal damage, several studies have shown that substances that block the process of trans-differentiation prevent EMT-induced fibrogenesis by mediating inflammation, oxidative stress, and apoptosis in renal tissues [ 12 , 27 ]. In gentamicin-induced nephrotoxicity, renal corpuscles and tubules pre-treated with resveratrol exhibit restored glutathione and catalase activity, decreased malondialdehyde content, increased E-cadherin expression, and decreased expression of α-SMA, TGF-β, and collagen [ 10 ]. The kidneys of UUO mice treated with ruxolitinib were observed to have lower levels of collagen deposition, α-SMA activation, TGF-β expression, inflammatory responses, malondialdehyde, and cleaved caspase-3 as well as elevated total superoxide dismutase arising from attenuation of ERK and Stat3 phosphorylation [ 11 ].Taken together, in this study we found that fraxetin had anti-fibrotic effects by decreasing the expression of α-SMA, collagen, N-cadherin and vimentin through down-regulation of the ERK signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…During the EMT, kidney tubule cells lose their epithelial characteristics and adopt a mesenchymal phenotype [ 8 , 9 ]. Studies show that blocking the trans-differentiation of renal tubule cells prevents EMT-induced inflammation, oxidative stress, and apoptosis by mediating transforming growth factor β (TGF-β) pathways [ 10 , 11 , 12 ]. Oxidative stress, inflammation, and the EMT are also caused by the uremic toxin indoxyl sulfate, a tryptophan metabolite that accumulates during CKD progression.…”

Section: Introductionmentioning

confidence: 99%

In Vitro and In Vivo Antifibrotic Effects of Fraxetin on Renal Interstitial Fibrosis via the ERK Signaling Pathway

Hsieh

Hung

Chen

et al. 2021

Toxins

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Fraxetin, a natural derivative of coumarin, is known to have anti-inflammatory, anti-oxidant, and hepatoprotective effects in multiple diseases and in liver fibrosis. Whether fraxetin exerts similar effects against renal fibrosis is unknown. In a Unilateral Ureteral Obstruction (UUO) mouse model of renal fibrosis, fraxetin decreased UUO-induced renal dysfunction with a marked reduction in renal interstitial collagen fibers as detected by Masson’s Trichrome staining. Fraxetin treatment also inhibited the expression of α-SMA, Collagen I, Collagen IV, fibronectin, N-cadherin, vimentin, phosphorylated-ERK, and increased the expression of E-cadherin in UUO mice, as shown by immunohistochemical staining and western blot analysis. In vitro studies showed that fraxetin and indoxyl sulfate had no cytotoxic effects on MES13 kidney cells, but that fraxetin significantly decreased IS-induced cell motility and decreased protein expression of α-SMA, N-cadherin, vimentin, and Collagen IV via the ERK-mediated signaling pathway. These findings provide insight into the mechanism underlying fraxetin-induced inhibition of fibrogenesis in renal tissue and suggest that fraxetin treatment may be beneficial for slowing CKD progression.

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Resveratrol reduces gentamicin-induced EMT in the kidney via inhibition of reactive oxygen species and involving TGF-β/Smad pathway

Cited by 44 publications

References 55 publications

Neutrophil extracellular DNA traps promote pancreatic cancer cells migration and invasion by activating EGFR/ERK pathway

Neutrophil extracellular DNA traps promote pancreatic cancer cells migration and invasion by activating EGFR/ERK pathway

D‐Limonene Alleviates Acute Kidney Injury Following Gentamicin Administration in Rats: Role of NF‐κB Pathway, Mitochondrial Apoptosis, Oxidative Stress, and PCNA

In Vitro and In Vivo Antifibrotic Effects of Fraxetin on Renal Interstitial Fibrosis via the ERK Signaling Pathway

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