Ghrelin modulates intracellular signalling pathways that are critical for podocyte survival

Zein, Nabil El; Abdallah, Maya; Daher, Costantine F.; Mroueh, Mohamad; Stephan, Joseph S.; Bahous, Sola Aoun; Eid, Assaad A.; Faour, Wissam H.

doi:10.1002/cbf.3397

Cited by 10 publications

(3 citation statements)

References 47 publications

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“…In the presence of IL-6, natural CD4 + T cells differentiate into Th17 cells (with TGF-α), instead of iTreg cells, which leads to a Th17/Treg cell imbalance. Research showed that high concentrations of IL-6 in sera and urine samples from SLE patients induced the degradation of Foxp3 and deregulation of Treg cells, possibly indicating a positive correlation with the severity of SLE [37,38]. Our previous studies suggested that a Th17/Treg imbalance was observed in the kidneys of LN mice, which resulted in increased levels of IL-6 and IL-17 and decreased concentration of Foxp3 [13].…”

Section: Discussionmentioning

confidence: 94%

Depletion of Fractalkine Ameliorates Renal Injury and Treg Cell Apoptosis Via the p38MAPK Pathway in Lupus-prone Mice

Gong

Guo

et al. 2020

Preprint

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Background: Fractalkine is a chemokine with several roles, including chemotaxis, adhesion, and immune damage. It participates in cell inflammation and apoptosis and responds to the pathogenesis of autoimmune diseases. On the other hand, Treg cells are involved in autoimmune diseases. This study aimed to explore the regulatory mechanism of Fractalkine in renal injury and Treg apoptosis via the p38MAPK signalling pathway in lupus-prone mice. Methods: Lupus was induced in BALB/c female mice by injection of pristane. Then, CD4+ CD5+ Treg cells were isolated from the spleen of lupus mice. To deplete Fractalkine, first, mice received an injection of anti-Fractalkine antibody. Later, the transfection of Treg cells with Fractalkine siRNA was conducted. Lupus mice and Treg cells were treated with the p38MAPK inhibitor SB203580 and/or activator U-46619, respectively. The levels of urine protein, serum urea nitrogen, creatinine, and autoantibodies were measured from mouse samples, and renal histopathological features were analysed. The expression of Fractalkine, p-p38, Foxp3, IL-6, and IL-17 in the mouse kidney and Treg cells was detected. The levels of apoptosis and key apoptotic factors: Bax, Bcl-2, and Cyt-c in Treg cells were analysed. Results: The expression of Fractalkine, p-p38, IL-6, and IL-17 increased; meanwhile, that of Foxp3 decreased in the kidneys of mice with lupus. The depletion of Fractalkine and p38MAPK levels ameliorated proteinuria and renal functions and significantly reduced serum autoantibodies, renal Fractalkine, p-p38, IL-6, and IL-17 levels, while increasing renal Foxp3 concentration in lupus mice. The effects of Fractalkine knockdown (KD) and p38MAPK inhibitor on Treg cells, derived from lupus mice, were consistent with those observed in the kidneys. In addition, Fractalkine KD reduced cell apoptosis and suppressed the activation of p38MAPK signalling in Treg cells, derived from lupus mice. Meanwhile, the p38MAPK activator U-46619 had the opposite effect. Conclusion: Together, our data indicated that Fractalkine promoted the nephritis progression in lupus mice, most likely through the regulation of Treg cell apoptosis and activation of the p38MAPK signalling pathway. It suggested that targeting Fractalkine is a potential therapeutic strategy for treating LN.

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Section: Discussionmentioning

confidence: 94%

Depletion of Fractalkine Ameliorates Renal Injury and Treg Cell Apoptosis Via the p38MAPK Pathway in Lupus-prone Mice

Gong

Guo

et al. 2020

Preprint

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“…Ghrelin is an endogenous “brain-gut” peptide and is safe for humans. It could reduce apoptosis induced by various pathological stimuli, such as hydrogen peroxide and high glucose [ 14 , 26 , 27 ]. In this study, ghrelin significantly inhibited HG-induced cell oxidative stress and injury.…”

Section: Discussionmentioning

confidence: 99%

Ghrelin Mitigates High-Glucose-Induced Oxidative Damage and Apoptosis in Lens Epithelial Cells

Bai

Jiang

Zhao

et al. 2022

Journal of Diabetes Research

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Oxidative stress induced by high glucose (HG) plays an important role in the mechanism of diabetic cataract. Evidence has shown that effects from oxidative stress induced damage of lens or human lens epithelial (HLE) cells. Antioxidant supplementation is a plausible strategy to avoid oxidative stress and maintain the function of lens. Ghrelin have been used in treatment of many diseases. In this study, we found that ghrelin attenuated HG-induced loss of cell viability, reduced oxidative damage, and cell apoptosis in HLE cells. Ghrelin inhibited apoptosis through the downregulation of Bax and the upregulation of Bcl-2. Our results suggest that ghrelin could be considered as a promising therapeutic intervention for diabetic cataract. We also observed rat lens transparent in cultured media and examined lens histopathological changes. The results showed that ghrelin could inhibit the histopathological injury of lenses and ultrastructural changes induced by HG. In conclusion, ghrelin may play a role in the treatment of ocular diseases involving diabetic cataract.

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“…Petri dishes were used to culture and treat MDA-MB-231 cells (2 × 10 5 cells/mL) with AELE (261 and 522 μg/ mL) for 24 h. The Qproteome mammalian protein prep kit (Qiagen, Hildren, Germany) was used to extract the proteins, which were then quantified based on the Lowry method. Proteins were prepared for separation by Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (10%) as explained by El Zein et al [41], and transferred to Polyvinylidene fluoride membranes for protein assessment, as previously described [42]. Membranes were incubated with primary antibodies (1:1000) anti-cytochrome c (Abcam, Cambridge, UK), anti-p21 (Cell Signaling, Danvers, MA), anti-Bax and anti-Bcl2 (Elabscience, Houston, TX, USA).…”

Section: Western Blotmentioning

confidence: 99%

The selective anti-proliferative and pro-apoptotic effect of A. cherimola on MDA-MB-231 breast cancer cell line

Younes

Ammoury

Haykal

et al. 2020

BMC Complement Med Ther

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Background Herbal medicines have been a major target for numerous studies through the past years as an alternative treatment for cancer, mainly due to their minimal effects on normal healthy cells. Annona cherimola, popularly known as Cherimoya, is an edible natural fruit rich in phytochemical components and known to possess various biological activities. Previous studies have reported the anti-cancerous effect of A. cherimola ethanolic leaf extract (AELE) on leukemia. This study aims at studying the potential anti-cancer activity of this extract in vitro in two different breast cancer cell lines, namely MDA-MB-231 and MCF-7, in addition to investigating its toxicity on normal mesenchymal stem cells. Methods The anti-proliferative effect of AELE was evaluated via cell viability assay. Propidium iodide staining, Cell Death Detection ELISA and flow cytometry analysis of Annexin V binding were used to assess cell cycle progression, DNA fragmentation and apoptosis induction, respectively. Protein expression was determined via Western Blot analysis to decipher the underlying apoptotic molecular mechanism induced upon AELE treatment. Results The anti-proliferative effect of the extract was found to be selective on the triple-negative breast cancer cell line (MDA-MB-231) in a time- and dose-dependent manner with an IC50 of 390.2 μg/mL at 48 h, with no cytotoxic effects on normal murine mesenchymal stem cells. The pro-apoptotic effect was confirmed by the increase in cellular and DNA fragmentation, flipping of the phosphatidylserine moiety to the outer leaflet, and the increase in Annexin V binding. The underlying molecular mechanism revealed the involvement of the mitochondrial pathway, as shown by alterations in mitochondrial permeability and the upregulation of cytochrome c expression. Conclusion All the data presented in our study suggest that AELE exhibits a selective anti-proliferative and pro-apoptotic effect on the chemo-resistant MDA-MB-231 breast cancer cells, providing evidence for the anti-tumor effects of A. cherimola.

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Ghrelin modulates intracellular signalling pathways that are critical for podocyte survival

Cited by 10 publications

References 47 publications

Depletion of Fractalkine Ameliorates Renal Injury and Treg Cell Apoptosis Via the p38MAPK Pathway in Lupus-prone Mice

Depletion of Fractalkine Ameliorates Renal Injury and Treg Cell Apoptosis Via the p38MAPK Pathway in Lupus-prone Mice

Ghrelin Mitigates High-Glucose-Induced Oxidative Damage and Apoptosis in Lens Epithelial Cells

The selective anti-proliferative and pro-apoptotic effect of A. cherimola on MDA-MB-231 breast cancer cell line

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