Increased expression and apical targeting of renal ENaC subunits in puromycin aminonucleoside-induced nephrotic syndrome in rats

Kim, Soo Wan; Wang, Weidong; Nielsen, Jens Perch; Prætorius, Jeppe; Kwon, Tae‐Hwan; Knepper, Mark A.; Frøkiær, Jørgen; Nielsén, Sören

doi:10.1152/ajprenal.00277.2003

Cited by 84 publications

(132 citation statements)

References 49 publications

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“…Affinity-purified rabbit polyclonal antibodies were used against the renal sodium transporters; NHE3, Na-K-ATPase a1 and the thiazide-sensitive Na + :Cl À cotransporter (NCC). 18 Affinity-purified rabbit polyclonal antibodies to TGF-b1 (Santa Cruz Biotechnology, Santa Cruz, CA, USA), ED-1 (Serotec, Raleigh, NC, USA), cyclooxygenase-2 (COX-2, Cayman Chemical, Ann Arbor, MI, USA), heat shock protein 25 (HSP25, Upstate Biotechnology, Lake Placid, NY, USA) and b-actin (Sigma, St Louis, MO, USA) were commercially obtained.…”

Section: Semiquantitative Immunoblottingmentioning

confidence: 99%

Rosiglitazone prevents the progression of renal injury in DOCA-salt hypertensive rats

et al. 2010

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This study was designed to evaluate the possible renoprotective effects of rosiglitazone (RGT), a peroxisome proliferatoractivated subtype c receptor agonist, in deoxycorticosterone acetate (DOCA)-salt hypertension and its role in endogenous endothelin-1 (ET-1) production and renal fibrosis associated with inflammation. Rats were implanted with DOCA strips (200 mg kg À1 ) at 1 week after unilateral nephrectomy. DOCA-salt rats received control diet with or without RGT (10 mg kg À1 per day). Systolic blood pressure was measured by the tail-cuff method. Glomerulosclerosis and tubulointerstitial fibrosis were evaluated on kidney sections. The expression of ED-1, cyclooxygenase-2 (COX-2), heat shock protein-25 (HSP25) and transforming growth factor-b1 (TGF-b1) was determined in the kidney by semiquantitative immunoblotting. In DOCA-salt rats, systolic blood pressure was increased, whereas creatinine clearance decreased compared with controls, which were counteracted by RGT treatment. Tubular injury and glomerulosclerois in the histological study were prominent in DOCA-salt rats, which were counteracted by RGT treatment. ET-1 expression was increased in DOCA-salts rats, which was attenuated by RGT treatment. The expression of TGF-b1, ED-1 and COX-2 was increased in DOCA-salt, which was attenuated by RGT treatment. In conclusion, RGT treatment decreases blood pressure and is effective in preventing the progression of renal injury in DOCA-salt hypertension, the mechanisms of which are associated with anti-inflammatory and anti-fibrotic effects through reducing the overexpression of ET-1, ED-1, COX-2 and TGF-b1 in the kidney.

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Section: Semiquantitative Immunoblottingmentioning

confidence: 99%

Rosiglitazone prevents the progression of renal injury in DOCA-salt hypertensive rats

et al. 2010

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“…The difference in weight represented the weight of the collected peritoneal fluid. Blood was collected from the inferior vena cava and analyzed for bilirubin, alanine aminotransaminase (ALT), Na ϩ , K ϩ , creatinine, osmolality, and plasma aldosterone concentration using methods described previously in detail (24). The right kidney was rapidly removed, dissected into three zones (cortex and outer stripe of outer medulla [OSOM], inner stripe of outer medulla [ISOM], and inner medulla) and processed for immunoblotting as described below.…”

Section: Experimental Protocolsmentioning

confidence: 99%

Increased Apical Targeting of Renal Epithelial Sodium Channel Subunits and Decreased Expression of Type 2 11β-Hydroxysteroid Dehydrogenase in Rats with CCl4-Induced Decompensated Liver Cirrhosis

Kim¹,

Schou²,

Peters³

et al. 2005

Journal of the American Society of Nephrology

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It was hypothesized that dysregulation of renal epithelial sodium channel (ENaC) subunits and/or 11␤-hydroxysteroid dehydrogenase (11␤HSD2) may play a role in the increased sodium retention in liver cirrhosis (LC). Experimental LC was induced in rats by CCl 4 (1 ml/kg, intraperitoneally, twice a week) for 12 wk (protocol 1) or for 11 wk (protocol 2). In both protocols, one group of rats with cirrhosis showed significantly decreased urinary sodium excretion and urinary Na/K ratio (group A), whereas a second group exhibited normal urinary sodium excretion (group B) compared with controls, even though extensive ascites was seen in both groups of rats with cirrhosis. In group A, protein abundance of ␣-ENaC was unchanged, whereas ␤-ENaC abundance was decreased in the cortex/outer stripe of outer medulla compared with controls. The ␥-ENaC underwent a complex change associated with increased abundance of the 70-kD band with a concomitant decrease in the main 85-kD band, corresponding to an aldosterone effect. In contrast, no changes in the abundance of ENaC subunit were observed in group B. Immunoperoxidase microscopy revealed an increased apical targeting of ␣-, ␤-, and ␥-ENaC subunits in distal convoluted tubule (DCT2), connecting tubule (CNT), and cortical and medullary collecting duct segments in group A but not in group B. Immunolabeling intensity of 11␤HSD2 in the DCT2, CNT, and cortical collecting duct was significantly reduced in group A but not in group B, and this was confirmed by immunoblotting. In conclusion, increased apical targeting of ENaC subunits combined with diminished abundance of 11␤HSD2 in the DCT2, CNT, and cortical collecting duct is likely to play a role in the sodium retaining stage of liver cirrhosis.

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“…33 Along with the uncertainties concerning the role aldosterone and MR, there is no consensus either on the renal site of sodium retention. Although several reports in experimental models of cirrhosis show that sodium retention originates along the aldosterone-sensitive nephron segments, 29,32,[34][35][36][37][38][39] other reports concluded to the thick ascending limb of Henle's loop as the main site of sodium retention in rat models. 40,41 The present study aimed at (1) localizing the site of sodium retention along the nephron, and (2) at determining the role of aldosterone and MR in sodium retention.…”

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Sodium retention and ascites formation in a cholestatic mice model: Role of aldosterone and mineralocorticoid receptor?

et al. 2007

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Renal sodium retention in experimental liver cirrhosis originates from the distal nephron sensitive to aldosterone. The aims of this study were to (1) determine the exact site of sodium retention along the aldosterone-sensitive distal nephron, and (2) to evaluate the role of aldosterone and mineralocorticoid receptor activation in this process. Liver cirrhosis was induced by bile duct ligation in either adrenalintact or corticosteroid-clamped mice. Corticosteroid-clamp was achieved through adrenalectomy and corticosteroid supplementation with aldosterone and dexamethasone via osmotic minipumps. 24-hours renal sodium balance was evaluated in metabolic cages. Activity and expression of sodiumand potassium-dependent adenosine triphosphatase were determined in microdissected segments of nephron. Within 4-5 weeks, cirrhosis induced sodium retention in adrenal-intact mice and formation of ascites in 50% of mice. At that time, sodium-and potassium-dependent adenosine triphosphatase activity increased specifically in cortical collecting ducts. Hyperaldosteronemia was indicated by increases in urinary aldosterone excretion and in sgk1 (serum-and glucocorticoid-regulated kinase 1) mRNA expression in collecting ducts. Corticosteroid-clamp prevented induction of sgk1 but not cirrhosis-induced sodium retention, formation of ascites and stimulation of sodium-and potassiumdependent adenosine triphosphatase activity and expression (mRNA and protein) in collecting duct. These findings demonstrate that sodium retention in cirrhosis is independent of hyperaldosteronemia and of the activation of mineralocorticoid receptor. Conclusion: Bile duct ligation in mice induces cirrhosis which, within 4-5 weeks, leads to the induction of sodium-and potassium-dependent adenosine triphosphatase in cortical collecting ducts, to renal sodium retention and to the formation of ascites. Sodium retention, ascites formation and induction of sodium-and potassium-dependent adenosine triphosphatase are independent of the activation of mineralocorticoid receptors by either aldosterone or glucocorticoids. (HEPATOLOGY 2007;46:173-179.) See Editorial on Page 9 P atients with liver cirrhosis and portal hypertension develop renal sodium retention which promotes formation of ascites and peripheral edema. The "underfill theory" initially attributed sodium retention to secondary hyperaldosteronism accounted for by renal hypoperfusion brought about by intraabdominal fluid sequestration. 1 However, the underfill theory cannot explain the early phase of cirrhosis as sodium retention may precedes formation of ascites. 2-7 Thus, the "overflow theory" postulated that edema and ascites formation resulted from primary renal sodium retention promoting plasma volume expansion. 8 This theory is supported by the fact that abolishing portal hypertension in cirrhotic dogs by sideto-side portocaval shunt prevented ascites formation but not sodium retention. 5,6 Later, the "revised underfill theory" proposed that peripheral arterial vasodilatation leading to decreased effec...

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Increased expression and apical targeting of renal ENaC subunits in puromycin aminonucleoside-induced nephrotic syndrome in rats

Abstract: . Increased expression and apical targeting of renal ENaC subunits in puromycin aminonucleoside-induced nephrotic syndrome in rats.

Cited by 84 publications

References 49 publications

Rosiglitazone prevents the progression of renal injury in DOCA-salt hypertensive rats

Rosiglitazone prevents the progression of renal injury in DOCA-salt hypertensive rats

Increased Apical Targeting of Renal Epithelial Sodium Channel Subunits and Decreased Expression of Type 2 11β-Hydroxysteroid Dehydrogenase in Rats with CCl4-Induced Decompensated Liver Cirrhosis

Sodium retention and ascites formation in a cholestatic mice model: Role of aldosterone and mineralocorticoid receptor?

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