The Experts below are selected from a list of 81 Experts worldwide ranked by ideXlab platform
Tobias E Larsson - One of the best experts on this subject based on the ideXlab platform.
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targeted deletion of klotho in Kidney Distal Tubule disrupts mineral metabolism
Journal of The American Society of Nephrology, 2012Co-Authors: Hannes Olauson, Karolina Lindberg, Risul Amin, Annika Wernerson, Goran Andersson, Tobias E LarssonAbstract:Renal Klotho controls mineral metabolism by directly modulating tubular reabsorption of phosphate and calcium and by acting as a co-receptor for the phosphaturic and vitamin D-regulating hormone fibroblast growth factor-23 (FGF23). Klotho null mice have a markedly abnormal phenotype. We sought to determine effects of renal-specific and partial deletion of Klotho to facilitate investigation of its roles in health and disease. We generated a mouse model with partial deletion of Klotho in Distal tubular segments (Ksp-KL(-/-)). In contrast to Klotho null mice, Ksp-KL(-/-) mice were fertile, had a normal gross phenotype, and did not have vascular or tubular calcification on renal histology. However, Ksp-KL(-/-) mice were hyperphosphatemic with elevated FGF23 levels and abundant expression of the sodium-phosphate cotransporter Npt2a at the brush border membrane. Serum calcium and 1,25-dihydroxyvitamin D(3) levels were normal but parathyroid hormone levels were decreased. TRPV5 protein was reduced with a parallel mild increase in urinary calcium excretion. Renal expression of vitamin D regulatory enzymes and vitamin D receptor was higher in Ksp-KL(-/-) mice than controls, suggesting increased turnover of vitamin D metabolites and a functional increase in vitamin D signaling. There was a threshold effect of residual renal Klotho expression on FGF23: deletion of >70% of Klotho resulted in FGF23 levels 30-250 times higher than in wild-type mice. A subgroup of Ksp-KL(-/-) mice with normal phosphate levels had elevated FGF23, suggesting a Klotho-derived renal-bone feedback loop. Taken together, renal FGF23-Klotho signaling, which is disrupted in CKD, is essential for homeostatic control of mineral metabolism.
Lucie Parent - One of the best experts on this subject based on the ideXlab platform.
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pH and external Ca 2+ regulation of a small conductance Cl − channel in Kidney Distal Tubule
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2020Co-Authors: Remy Sauve, Line Garneau, Helene Klein, Lucie ParentAbstract:AbstractA single channel characterization of the Cl− channels in Distal nephron was undertaken using vesicles prepared from plasma membranes of isolated rabbit Distal Tubules. The presence in this vesicle preparation of ClC-K type Cl− channels was first established by immunodetection using an antibody raised against ClC-K isoforms. A ClC-K1 based functional characterization was next performed by investigating the pH and external Ca2+ regulation of a small conductance Cl− channel which we identified previously by channel incorporation experiments. Acidification of the cis (external) solution from pH 7.4 to 6.5 led to a dose-dependent inhibition of the channel open probability PO. Similarly, changing the trans pH from 7.4 to 6.8 resulted in a 4-fold decrease of the channel PO with no effect on the channel conductance. Channel activity also appeared to be regulated by cis (external) Ca2+ concentration, with a dose-dependent increase in channel activity as a function of the cis Ca2+ concentration. It is concluded on the basis of these results that the small conductance Cl− channel present in rabbit Distal Tubules is functionally equivalent to the ClC-K1 channel in the rat. In addition, the present work constitutes the first single channel evidence for a chloride channel regulated by external Ca2+
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ph and external ca 2 regulation of a small conductance cl channel in Kidney Distal Tubule
Biochimica et Biophysica Acta, 2000Co-Authors: Remy Sauve, Line Garneau, Helene Klein, Lucie ParentAbstract:Abstract A single channel characterization of the Cl− channels in Distal nephron was undertaken using vesicles prepared from plasma membranes of isolated rabbit Distal Tubules. The presence in this vesicle preparation of ClC-K type Cl− channels was first established by immunodetection using an antibody raised against ClC-K isoforms. A ClC-K1 based functional characterization was next performed by investigating the pH and external Ca2+ regulation of a small conductance Cl− channel which we identified previously by channel incorporation experiments. Acidification of the cis (external) solution from pH 7.4 to 6.5 led to a dose-dependent inhibition of the channel open probability PO. Similarly, changing the trans pH from 7.4 to 6.8 resulted in a 4-fold decrease of the channel PO with no effect on the channel conductance. Channel activity also appeared to be regulated by cis (external) Ca2+ concentration, with a dose-dependent increase in channel activity as a function of the cis Ca2+ concentration. It is concluded on the basis of these results that the small conductance Cl− channel present in rabbit Distal Tubules is functionally equivalent to the ClC-K1 channel in the rat. In addition, the present work constitutes the first single channel evidence for a chloride channel regulated by external Ca2+.
L. Darryl Quarles - One of the best experts on this subject based on the ideXlab platform.
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Cardiovascular Effects of Renal Distal Tubule Deletion of the FGF Receptor 1 Gene.
Journal of The American Society of Nephrology, 2017Co-Authors: Jed Ross, Ganesh Kolumam, Junichiro Sonoda, Min Pi, Gwendalyn D. King, L. Darryl QuarlesAbstract:The bone-derived hormone fibroblast growth factor–23 (FGF-23) activates complexes composed of FGF receptors (FGFRs), including FGFR1, and α -Klotho in the Kidney Distal Tubule (DT), leading to increased sodium retention and hypertension. However, the role of FGFR1 in regulating renal processes linked to hypertension is unclear. Here, we investigated the effects of selective FGFR1 loss in the DT. Conditional knockout (cKO) of FGFR1 in the DT ( FGFR1 DT-cKO mice) resulted in left ventricular hypertrophy (LVH) and decreased Kidney expression of α -Klotho in association with enhanced BP, decreased expression of angiotensin converting enzyme 2, and increased expression of the Na + -K + -2Cl − cotransporter. Notably, recombinant FGF-23 administration similarly decreased the Kidney expression of α -Klotho and induced LVH in mice. Pharmacologic activation of FGFR1 with a monoclonal anti-FGFR1 antibody (R1MAb1) normalized BP and significantly attenuated LVH in the Hyp mouse model of excess FGF-23, but did not induce a response in FGFR1 DT-cKO mice. The hearts of FGFR1 DT-cKO mice showed increased expression of the transient receptor potential cation channel, subfamily C, member 6 (TRPC6), consistent with cardiac effects of soluble Klotho deficiency. Moreover, administration of recombinant soluble Klotho lowered BP in the Hyp mice. Thus, FGFR1 in the DT regulates systemic hemodynamic responses opposite to those predicted by the actions of FGF-23. These cardiovascular effects appear to be mediated by paracrine FGF control of Kidney FGFR1 and subsequent regulation of soluble Klotho and TRPC6. FGFR1 in the Kidney may provide a new molecular target for treating hypertension.
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Cardiovascular Effects of Renal Distal Tubule Deletion of the FGF Receptor 1 Gene
Journal of the American Society of Nephrology, 2017Co-Authors: Xiaobin Han, Gwendalyn King, Jed Ross, Ganesh Kolumam, Junichiro Sonoda, Min Pi, L. Darryl QuarlesAbstract:Copyright © 2018 by the American Society of Nephrology. The bone-derived hormone fibroblast growth factor–23 (FGF-23) activates complexes composed of FGF receptors (FGFRs), including FGFR1, and a-Klotho in the Kidney Distal Tubule (DT), leading to increased sodium retention and hypertension. However, the role of FGFR1 in regulating renal processes linked to hypertension is unclear. Here, we investigated the effects of selective FGFR1 loss in the DT. Conditional knockout (cKO) of FGFR1 in the DT (FGFR1 DT-cKO mice) resulted in left ventricular hypertrophy (LVH) and decreased Kidney expression of a-Klotho in association with enhanced BP, decreased expression of angiotensin converting enzyme 2, and increased expression of the Na + -K + -2Cl 2 cotransporter. Notably, recombinant FGF-23 administration similarly decreased the Kidney expression of a-Klotho and induced LVH in mice. Pharmacologic activation of FGFR1 with a monoclonal anti-FGFR1 antibody (R1MAb1) normalized BP and significantly attenuated LVH in the Hyp mouse model of excess FGF-23, but did not induce a response in FGFR1 DT-cKO mice. The hearts of FGFR1 DT-cKO mice showed increased expression of the transient receptor potential cation channel, subfamily C, member 6 (TRPC6), consistent with cardiac effects of soluble Klotho deficiency. Moreover, administration of recombinant soluble Klotho lowered BP in the Hyp mice. Thus, FGFR1 in the DT regulates systemic hemodynamic responses opposite to those predicted by the actions of FGF-23. These cardiovascular effects appear to be mediated by paracrine FGF control of Kidney FGFR1 and subsequent regulation of soluble Klotho and TRPC6. FGFR1 in the Kidney may provide a new molecular target for treating hypertension.
David H Ellison - One of the best experts on this subject based on the ideXlab platform.
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salt sensitive transcriptome of isolated Kidney Distal Tubule cells
Physiological Genomics, 2019Co-Authors: Elizabeth A Swanson, Jonathan W Nelson, Sophia Jeng, Kayla J Erspamer, Chao Ling Yang, Shannon K Mcweeney, David H EllisonAbstract:In the Distal Kidney Tubule, the steroid hormone aldosterone regulates sodium reabsorption via the epithelial sodium channel (ENaC). Most studies seeking to identify ENaC-regulating aldosterone-ind...
Remy Sauve - One of the best experts on this subject based on the ideXlab platform.
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pH and external Ca 2+ regulation of a small conductance Cl − channel in Kidney Distal Tubule
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2020Co-Authors: Remy Sauve, Line Garneau, Helene Klein, Lucie ParentAbstract:AbstractA single channel characterization of the Cl− channels in Distal nephron was undertaken using vesicles prepared from plasma membranes of isolated rabbit Distal Tubules. The presence in this vesicle preparation of ClC-K type Cl− channels was first established by immunodetection using an antibody raised against ClC-K isoforms. A ClC-K1 based functional characterization was next performed by investigating the pH and external Ca2+ regulation of a small conductance Cl− channel which we identified previously by channel incorporation experiments. Acidification of the cis (external) solution from pH 7.4 to 6.5 led to a dose-dependent inhibition of the channel open probability PO. Similarly, changing the trans pH from 7.4 to 6.8 resulted in a 4-fold decrease of the channel PO with no effect on the channel conductance. Channel activity also appeared to be regulated by cis (external) Ca2+ concentration, with a dose-dependent increase in channel activity as a function of the cis Ca2+ concentration. It is concluded on the basis of these results that the small conductance Cl− channel present in rabbit Distal Tubules is functionally equivalent to the ClC-K1 channel in the rat. In addition, the present work constitutes the first single channel evidence for a chloride channel regulated by external Ca2+
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ph and external ca 2 regulation of a small conductance cl channel in Kidney Distal Tubule
Biochimica et Biophysica Acta, 2000Co-Authors: Remy Sauve, Line Garneau, Helene Klein, Lucie ParentAbstract:Abstract A single channel characterization of the Cl− channels in Distal nephron was undertaken using vesicles prepared from plasma membranes of isolated rabbit Distal Tubules. The presence in this vesicle preparation of ClC-K type Cl− channels was first established by immunodetection using an antibody raised against ClC-K isoforms. A ClC-K1 based functional characterization was next performed by investigating the pH and external Ca2+ regulation of a small conductance Cl− channel which we identified previously by channel incorporation experiments. Acidification of the cis (external) solution from pH 7.4 to 6.5 led to a dose-dependent inhibition of the channel open probability PO. Similarly, changing the trans pH from 7.4 to 6.8 resulted in a 4-fold decrease of the channel PO with no effect on the channel conductance. Channel activity also appeared to be regulated by cis (external) Ca2+ concentration, with a dose-dependent increase in channel activity as a function of the cis Ca2+ concentration. It is concluded on the basis of these results that the small conductance Cl− channel present in rabbit Distal Tubules is functionally equivalent to the ClC-K1 channel in the rat. In addition, the present work constitutes the first single channel evidence for a chloride channel regulated by external Ca2+.
