Aldosterone signaling regulates the over-expression of claudin-4 and -8 at the distal nephron from type 1 diabetic rats

Molina‐Jijón, Eduardo; Rodríguez-Muñóz, Rafael; González‐Ramírez, Ricardo; Namorado-Tónix, Carmen; Pedraza‐Chaverrí, José; Reyes, José L.

doi:10.1371/journal.pone.0177362

Cited by 18 publications

(14 citation statements)

References 54 publications

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“…These effects were mediated by a decrease in glucose‐6‐phosphate dehydrogenase activity (Pessôa et al, 2012). Spironolactone increased cloudin 2, 4, 5, and 8 by suppressing oxidative stress without altering serum glucose in T1DM rats (Molina‐Jijón et al, 2017). Eplerenone increased GLP‐1 in primary aldosteronism (Goto et al, 2019).…”

Section: Mr Antagonist In Diabetic Nephropathymentioning

confidence: 99%

Role of mineralocorticoid receptor antagonists in kidney diseases

Patel

Joharapurkar

Jain

2020

Drug Development Research

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Mineralocorticoid receptor (MR) antagonists, for example, spironolactone and eplerenone, are in clinical use to treat hypertension. Increasing evidence suggests that mineralocorticoid receptor activation causes the pathogenesis and progression of chronic kidney disease. Aldosterone‐induced MR activation increases inflammation, fibrosis, and oxidative stress in the kidney. MR antagonists (MRAs) have demonstrated therapeutic actions in chronic kidney disease (CKD), diabetic nephropathy (DN), renal fibrosis, and drug‐induced renal injury in preclinical and clinical studies. We have summarized and discussed these studies in this review. The nonsteroidal MRA, esaxerenone, recently received approval for the treatment of hypertension. It has also shown a positive therapeutic effect in phase 3 clinical trials in patients with DN. Other nonsteroidal MRA such as apararenone, finerenone, AZD9977, and LY2623091 are in different clinical trials in patients with hypertension suffering from renal or hepatic fibrotic diseases. Hyperkalemia associated with MRA therapy has frequently led to the discontinuation of the treatment. The new generation nonsteroidal MRAs like esaxerenone are less likely to cause hyperkalemia at therapeutic doses. It appears that the nonsteroidal MRAs can provide optimum therapeutic benefit for patients suffering from kidney diseases.

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Section: Mr Antagonist In Diabetic Nephropathymentioning

confidence: 99%

Role of mineralocorticoid receptor antagonists in kidney diseases

Patel

Joharapurkar

Jain

2020

Drug Development Research

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“… 34 suggest that claudin-8 has a function of preventing Na + back leakage from plasma to luminal fluid. The activation of MR by ALD increases the expression of claudins-4 and -8, and their localization in the TJs of ALD-sensitive distal nephron 36 . However, our data indicate that ALD did not increase the mRNA and protein levels of claudin-4 and -8 in MCE301 cells.…”

Section: Discussionmentioning

confidence: 95%

Up-regulation of claudin-2 expression by aldosterone in colonic epithelial cells of mice fed with NaCl-depleted diets

Furukawa

Ishizuka

Hayashi

et al. 2017

Sci Rep

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Dietary NaCl depletion increases Na+ absorption and K+ secretion in the colon, but the mechanisms are not fully understood. In mice fed with NaCl-depleted diets, the expression of claudin-2 and -7 increased compared to those in control mice. Aldosterone (ALD) concentration was also increased. We examined the regulatory mechanism of claudin expression by ALD using the murine colonic epithelial MCE301 cells. ALD dose-dependently increased claudin-2 expression without affecting the expression of claudin-4, -7, -8, and -15. ALD increased nuclear distribution of mineralocorticoid receptor (MR), which was inhibited by spironolactone, an MR antagonist. The ALD-induced elevation of claudin-2 mRNA and protein expression was inhibited by spironolactone, but not by RU-486, a glucocorticoid receptor antagonist. Luciferase reporter assay showed that ALD interacts with the promoter region between -2,021 and -2,008 of human claudin-2. The binding of MR on the promoter region of claudin-2 was increased by ALD, which was inhibited by spironolactone in chromatin immunoprecipitation assay. Our data suggest that ALD acts on MR and increases paracellular permeability to ions mediated by the elevation of claudin-2 expression in the colon. NaCl depletion may increase ALD secretion from adrenal cortex, resulting in the elevation of paracellular permeability to cations in the colon.

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“…Steroids acting through their genomic effects on steroid response element (SRE) in various genes have been shown to up- or down-regulates several genes related to serum and glucocorticoid kinase 1 (SGK-1) tight junction proteins (Claudin-4, Claudin-8, Claudin-2, Zonulin-1), ion channels (ENaC, ROMK/BK, TRPV4/5/6, TRPM 7/6) which may also impact renal function in a yet to be defined fashion. 25 , 26 …”

Section: Discussionmentioning

confidence: 99%

Postnatal glucocorticoid use impacts renal function in VLBW neonates

et al. 2021

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Background Preterm neonates often require glucocorticoids to manage refractory hypotension, prevent, and treat bronchopulmonary dysplasia. We have investigated the effect of cumulative dose and duration of glucocorticoids on blood pressure and renal function in VLBW infants. Methods In this retrospective cohort study, medical records of infants (GA ≤ 35 weeks) born January 2015 to December 2019 were reviewed to extract demographic and clinical characteristics, dose and duration of steroids, blood pressure (BP), and creatinine at the time of discharge from the neonatal intensive care unit. Results Two hundred and eighty-three neonates with average GA (28 ± 3 weeks) and birthweight (1060±381 g). Twenty-eight percent (33/116) of infants who received postnatal steroids developed hypertension versus 16% (27/167) of controls (OR = 2.0, p = 0.011). There was a correlation between the cumulative dosage of postnatal steroids and systolic BP ( R 2 = 0.06, p < 0.001). With increasing steroid dose and total steroid days, there was a significant increase in creatinine clearance at the time of discharge ( R 2 = 0.13, p < 0.001; R 2 = 0.13, p < 0.001, respectively). Conclusions Cumulative dose of postnatal steroids and duration of use is associated with increased systolic BP in premature infants. Postnatal steroids should be used prudently to prevent long-term cardiovascular and renal morbidity. Impact Preterm neonates are exposed to a high dose of glucocorticoids during their neonatal intensive care stay. The dose and duration of use of postnatal glucocorticoids was associated with significant increase in blood pressure at the time of discharge in preterm neonates. Postnatal glucocorticoid use is associated with improved creatinine clearance likely due to a state of hyperfiltration and may lead to chronic kidney disease later in life. Postnatal glucocorticoids should be used prudently in this highly vulnerable population

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Aldosterone signaling regulates the over-expression of claudin-4 and -8 at the distal nephron from type 1 diabetic rats

Cited by 18 publications

References 54 publications

Role of mineralocorticoid receptor antagonists in kidney diseases

Role of mineralocorticoid receptor antagonists in kidney diseases

Up-regulation of claudin-2 expression by aldosterone in colonic epithelial cells of mice fed with NaCl-depleted diets

Postnatal glucocorticoid use impacts renal function in VLBW neonates

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