Polycystin-1 dysfunction impairs electrolyte and water handling in a renal precystic mouse model for ADPKD

American Journal of Physiology. Renal Physiology
Eric H J VerschurenFrancisco J Arjona

Abstract

The PKD1 gene encodes polycystin-1 (PC1), a mechanosensor triggering intracellular responses upon urinary flow sensing in kidney tubular cells. Mutations in PKD1 lead to autosomal dominant polycystic kidney disease (ADPKD). The involvement of PC1 in renal electrolyte handling remains unknown since renal electrolyte physiology in ADPKD patients has only been characterized in cystic ADPKD. We thus studied the renal electrolyte handling in inducible kidney-specific Pkd1 knockout (iKsp- Pkd1-/-) mice manifesting a precystic phenotype. Serum and urinary electrolyte determinations indicated that iKsp- Pkd1-/- mice display reduced serum levels of magnesium (Mg2+), calcium (Ca2+), sodium (Na+), and phosphate (Pi) compared with control ( Pkd1+/+) mice and renal Mg2+, Ca2+, and Pi wasting. In agreement with these electrolyte disturbances, downregulation of key genes for electrolyte reabsorption in the thick ascending limb of Henle's loop (TA;, Cldn16, Kcnj1, and Slc12a1), distal convoluted tubule (DCT; Trpm6 and Slc12a3) and connecting tubule (CNT; Calb1, Slc8a1, and Atp2b4) was observed in kidneys of iKsp- Pkd1-/- mice compared with controls. Similarly, decreased renal gene expression of markers for TAL ( Umod) and DCT ( Pvalb) was obse...Continue Reading

References

May 1, 1987·Anaesthesia and Intensive Care·L I WorthleyR W Pain
Jan 1, 1996·Mayo Clinic Proceedings·C R FlemingT P Moyer
Sep 20, 2002·Journal of the American Society of Nephrology : JASN·Bradley K YoderLisa M Guay-Woodford
Oct 22, 2002·American Journal of Physiology. Renal Physiology·E Wolfgang KuehnJoseph V Bonventre
Feb 8, 2003·The EMBO Journal·J G J HoenderopR J M Bindels
Mar 28, 2003·Journal of the American Society of Nephrology : JASN·Rajeev RohatgiLisa M Satlin
Aug 19, 2005·Molecular Biology of the Cell·Alessandra ZattiMichael J Caplan
Oct 7, 2005·American Journal of Physiology. Cell Physiology·Dragos OlteanuErik M Schwiebert
Dec 2, 2005·Journal of the American Society of Nephrology : JASN·Tamio YamaguchiDarren P Wallace
Apr 8, 2006·Physiological Reviews·Linda J MullinsJohn J Mullins
May 4, 2007·Journal of the American Society of Nephrology : JASN·Ali K AhrabiOlivier Devuyst
Apr 3, 2009·Clinical Journal of the American Society of Nephrology : CJASN·José L NishiuraIta P Heilberg
Jul 31, 2009·Kidney International·John K MaesakaEkambaram Ilamathi
Oct 17, 2009·Journal of the American Society of Nephrology : JASN·Ana P BastosLuiz F Onuchic
Mar 12, 2010·Advances in Chronic Kidney Disease·Arlene B ChapmanFrederic Rahbari-Oskoui
Mar 25, 2010·Histochemistry and Cell Biology·József JászaiDenis Corbeil
Oct 21, 2010·Biochimica Et Biophysica Acta·Nadezhda N ZheleznovaAlexander Staruschenko
Nov 17, 2010·The Journal of Cell Biology·Hannah C Chapin, Michael J Caplan
Jan 25, 2011·Biochimica Et Biophysica Acta·Sara TerrynOlivier Devuyst
Sep 9, 2011·American Journal of Physiology. Renal Physiology·Gustavo R AresPablo A Ortiz
Jan 19, 2012·International Review of Cell and Molecular Biology·James A Deane, Sharon D Ricardo
Jan 20, 2012·Kidney International·Chirag R ParikhStefan Somlo
Feb 22, 2012·Journal of the American Society of Nephrology : JASN·Zlata NovalicDorien J M Peters
May 11, 2012·Journal of Nephrology·Ewout J HoornDavid H Ellison
Aug 11, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Titia E Woudenberg-VrenkenJoost G J Hoenderop
Oct 16, 2012·The Journal of Clinical Investigation·Katharina HoppPeter C Harris
Nov 13, 2012·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Eric OlingerOlivier Devuyst
Mar 8, 2013·Kidney International·Hester HappéDorien J M Peters
Mar 1, 2014·Journal of the American Society of Nephrology : JASN·Toshiro Fujita
Apr 5, 2014·PLoS Genetics·Francisco J ArjonaJoost G J Hoenderop
May 24, 2014·Clinical Journal of the American Society of Nephrology : CJASN·Arohan R Subramanya, David H Ellison
May 31, 2014·Clinical Journal of the American Society of Nephrology : CJASN·David PearceDonald E Kohan
Aug 20, 2014·Nature Reviews. Nephrology·Hester Happé, Dorien J M Peters
Oct 17, 2014·Clinical Journal of the American Society of Nephrology : CJASN·David B Mount
Nov 2, 2014·Journal of the American Society of Nephrology : JASN·Wouter N LeonhardDorien J M Peters
Nov 18, 2014·The New England Journal of Medicine·Robert W SchrierUNKNOWN HALT-PKD Trial Investigators
Dec 30, 2014·Physiological Reviews·Jeroen H F de BaaijRené J M Bindels
Jan 20, 2015·AIMS Molecular Science·Sarmed H KathemSurya M Nauli

❮ Previous
Next ❯

Citations

Jan 1, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Eric H J VerschurenRené J M Bindels
Mar 12, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Eric H J VerschurenJoost G J Hoenderop
Apr 18, 2020·Journal of the American Society of Nephrology : JASN·Jayalakshmi LakshmipathiDonald E Kohan
Mar 5, 2020·Nature Reviews. Nephrology·Eric H J VerschurenJoost G J Hoenderop
May 29, 2021·Journal of the American Society of Nephrology : JASN·David H EllisonJames A McCormick
Jul 3, 2021·Nature Reviews. Nephrology·Emma T B Olesen, Robert A Fenton

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR

Software Mentioned

GraphPad Prism
ImageJ
Photoshop CC

Related Concepts

Related Feeds

Cachexia & Brown Fat

Cachexia is a condition associated with progressive weight loss due to severe illness. In cancer patients, it is proposed to occur as a result of tumor-induced energy wasting. Several proteins have been implicated in browning and depletion of white adipose tissue. Here is the latest research on cachexia and brown fat.

Cardiac Cachexia

Cardiac cachexia is a syndrome associated with the progressive loss of muscle and fat mass. It most commonly affects patients with heart failure and can significantly decrease the quality of life and survival in these patients. Here is the latest research on cardiac cachexia.