Inhibition of cellular transdifferentiation by losartan minimizes but does not reverse type 2 diabetes-induced renal fibrosis

Arnoni, Carine Prisco; Maquigussa, Edgar; Passos, Clévia Santos; Pereira, Luciana G.; Boim, Mirian Aparecida

doi:10.1177/1470320313497817

Cited by 8 publications

(6 citation statements)

References 48 publications

(56 reference statements)

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“…By following the pioneering hypothesis of Arnoni et al . 55 with slight modification, RF may be initiated by Bic in the initial stage via upregulating PDGFs; hence cell proliferation was completely halted (Fig. 1e), however the upregulation of PDGF-β was only noted significantly when Bic at doses of 60 μM (p < 0.05) in our results (Fig.…”

Section: Resultsmentioning

confidence: 51%

Renal Damaging Effect Elicited by Bicalutamide Therapy Uncovered Multiple Action Mechanisms As Evidenced by the Cell Model

Peng

Chen²,

Chen

et al. 2019

Sci Rep

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Bicalutamide (Bic) is frequently used in androgen deprivation therapy (ADT) for treating prostate cancer. ADT-induced hypogonadism was reported to have the potential to lead to acute kidney injury (AKI). ADT was also shown to induce bladder fibrosis via induction of the transforming growth factor (TGF)-β level. We hypothesized that Bic can likely induce renal fibrosis. To understand this, a cell model was used to explore expressions of relevant profibrotic proteins. Results indicated that Bic initiated multiple apoptotic and fibrotic pathways, including androgen deprivation, downregulation of the androgen receptor → phosphatidylinositol-3-kinase → Akt pathway, upregulation of the extrinsic apoptotic pathway- tumor necrosis factor α → nuclear factor κB → caspase-3, increased expressions of fibrosis-related proteins including platelet-derived growth factor β, fibronectin and collagen IV, and enhanced cell migration. The endoplasmic reticular stress pathway and smooth muscle actin were unaffected by Bic. Co-treatment with testosterone was shown to have an anti-apoptotic effect against Bic, suggesting a better outcome of Bic therapy if administered with an appropriate testosterone intervention. However, since Bic was found to inhibit the membrane transport and consumption rates of testosterone, a slightly larger dose of testosterone is recommended. In conclusion, these pathways can be considered to be pharmaceutically relevant targets for drug development in treating the adverse effects of Bic.

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Section: Resultsmentioning

confidence: 51%

Renal Damaging Effect Elicited by Bicalutamide Therapy Uncovered Multiple Action Mechanisms As Evidenced by the Cell Model

Peng

Chen²,

Chen

et al. 2019

Sci Rep

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“…Here, we aimed to provide data to determine the most suitable reference gene to be used for mesangial cells and podocytes exposed to a high glucose environment and treated with Losartan, a very known in vitro model for diabetic kidney disease (7,(22)(23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

Reference genes for mesangial cell and podocyte qPCR gene expression studies under high-glucose and renin-angiotensin-system blocker conditions

Hosni

Anauate

Boim

2021

Preprint

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BackgroundReal-time PCR remains currently the gold standard method for gene expression studies. Identification of the best reference gene is a key point in performing high quality qPCR, providing strong support for results, as well as performing as a source of bias when inappropriately chosen. Mesangial cells and podocytes, as essential cell lines to study diabetic kidney disease (DKD) physiopathology, demand accurate analysis of the reference genes used so far to enhance validity of gene expression studies, especially regarding high glucose (HG) and DKD treatments, with angiotensin II receptor blockers (e.g. Losartan) being the most commonly used. This study aimed to evaluate the suitability and define the most stable reference gene for mesangial cells and podocytes studies of an in vitro DKD model of disease and its treatment.MethodsFive software packages (RefFinder, NormFinder, GeNorm, Bestkeeper, and DataAssist) and the comparative ΔCt method were selected to analyze six different candidate genes: HPRT, ACTB, PGAM-1, GAPDH, PPIA, and B2M. RNA was extracted and cDNA was synthesized from immortalized mouse mesangial cells and podocytes cultured in 4 groups: control (n=5; 5mM glucose), mannitol (n=5; 30mM, as osmotic control), HG (n=5; 30mM glucose), and HG + losartan (n=5; 30mM glucose and 10-4 mM of losartan). Real-time PCR was performed according to MIQE guidelines.ResultsWe identified that the use of 2 genes is the best combination for qPCR normalization for both mesangial cell and podocytes. For mesangial cells, the combination of HPRT and ACTB presented higher stability values. For podocytes, HPRT and GAPDH showed the best results.ConclusionThis analysis provides support for the use of HPRT and ACTB as reference genes in mouse mesangial cell studies of gene expression via real-time PCR technique, while for podocytes, HPRT and GAPDH should be chosen.

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“…Here, we aimed to provide data to determine the most suitable reference gene to be used for PLOS ONE mesangial cells and podocytes exposed to a high glucose environment and treated with losartan, a very known in vitro model for diabetic kidney disease [7,[28][29][30][31].…”

Section: Discussionmentioning

confidence: 99%

Reference genes for mesangial cell and podocyte qPCR gene expression studies under high-glucose and renin-angiotensin-system blocker conditions

2021

View full text Add to dashboard Cite

Background Real-time PCR remains currently the gold standard method for gene expression studies. Identification of the best reference gene is a key point in performing high-quality qPCR, providing strong support for results, and performing as a source of bias when inappropriately chosen. Mesangial cells and podocytes, as essential cell lines to study diabetic kidney disease (DKD) physiopathology, demand accurate analysis of the reference genes used thus far to enhance the validity of gene expression studies, especially regarding high glucose (HG) and DKD treatments, with angiotensin II receptor blockers (e.g., losartan) being the most commonly used. This study aimed to evaluate the suitability and define the most stable reference gene for mesangial cell and podocyte studies of an in vitro DKD model of disease and its treatment. Methods Five software packages (RefFinder, NormFinder, GeNorm, Bestkeeper, and DataAssist) and the comparative ΔCt method were selected to analyze six different candidate genes: HPRT, ACTB, PGAM-1, GAPDH, PPIA, and B2M. RNA was extracted, and cDNA was synthesized from immortalized mouse mesangial cells and podocytes cultured in 4 groups: control (n = 5; 5 mM glucose), mannitol (n = 5; 30 mM, as osmotic control), HG (n = 5; 30 mM glucose), and HG + losartan (n = 5; 30 mM glucose and 10−4 mM losartan). Real-time PCR was performed according to MIQE guidelines. Results We identified that the use of 2 genes was the best combination for qPCR normalization for both mesangial cells and podocytes. For mesangial cells, the combination of HPRT and ACTB presented higher stability values. For podocytes, HPRT and GAPDH showed the best results. Conclusion This analysis provides support for the use of HPRT and ACTB as reference genes in mouse mesangial cell studies of gene expression via real-time PCR, while for podocytes, HPRT and GAPDH should be chosen.

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Inhibition of cellular transdifferentiation by losartan minimizes but does not reverse type 2 diabetes-induced renal fibrosis

Cited by 8 publications

References 48 publications

Renal Damaging Effect Elicited by Bicalutamide Therapy Uncovered Multiple Action Mechanisms As Evidenced by the Cell Model

Renal Damaging Effect Elicited by Bicalutamide Therapy Uncovered Multiple Action Mechanisms As Evidenced by the Cell Model

Reference genes for mesangial cell and podocyte qPCR gene expression studies under high-glucose and renin-angiotensin-system blocker conditions

Reference genes for mesangial cell and podocyte qPCR gene expression studies under high-glucose and renin-angiotensin-system blocker conditions

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