Our main interest is focused on the mechanisms that allow kidney to adapt its functions to the physiological environment. More precisely, these last years, we have investigated how the kidney maintain potassium balance 1/ under dietary K+ restriction 2/ during gestation and 3/ during activity-rest alternance (circadian rhythm).
These studies highlighted the fact that a renal ion transporter named H,K-ATPase type 2 (HKA2 also known as the “non-gastric” or the “colonic” H,K-ATPase) has to be stimulated in order to preserve plasma K+ parameters in all three situations mentioned above (Figure 1).
Moreover, we described a new renal regulatory pathway involving progesterone, HKA2 and renal K+ retention. We used methods involving molecular biology techniques, cell culture, normal and genetically-modified mouse models and metabolic analysis.
Figure 1: Summary of the physiological contexts in which H,K-ATPase type 2 is involved.
Gilles Crambert: CR1 CNRS
Christne Lamouroux : Engineer
Renal potassium handling in carriers of the Gly40Ser mutation of the glucagon receptor suggests a role for glucagon in potassium homeostasis. Bankir L, Barbato A, Russo O, Crambert G, Iacone R, Bouby N, Perna L, Strazzullo P. Physiol Rep. 2018 Apr;6(8):e13661. PMID: 29671960
Versatility of NaCl transport mechanisms in the cortical collecting duct. Edwards A, Crambert G. Am J Physiol Renal Physiol. 2017 Dec 1;313(6):F1254-F1263. PMID: 28877883
H,K-ATPase type 2 contributes to salt-sensitive hypertension induced by K(+) restriction. Walter C, Tanfous MB, Igoudjil K, Salhi A, Escher G, Crambert G. Pflugers Arch. 2016 Oct;468(10):1673-83. PMID : 27562425
The renal cortical collecting duct: a secreting epithelium? Morla L, Doucet A, Lamouroux C, Crambert G, Edwards A. J Physiol. 2016 Oct 15;594(20):5991-6008. PMID: 27412964
Glucagon actions on the kidney revisited: possible role in potassium homeostasis. Bankir L, Bouby N, Blondeau B, Crambert G. Am J Physiol Renal Physiol. 2016 Aug 1;311(2):F469-86. PMID: 27194722
New insights into sodium transport regulation in the distal nephron: Role of G-protein coupled receptors. Morla L, Edwards A, Crambert G. World J Biol Chem. 2016 Feb 26;7(1):44-63. PMID: 26981195
Epithelial sodium channel abundance is decreased by an unfolded protein response induced by hyperosmolality. G. Crambert, T. Ernandez, C. Lamouroux, I. Roth, E. Dizin, P.Y. Martin, E. Feraille AND U. Hasler. Physiol Rep. 2014 Nov 20;2(11). PMID: 25413317
H,K-ATPase type 2: relevance for renal physiology and beyond. G. CRAMBERT. AJP Renal. (2014) 306,F693-F700. PMID:24431203
A link between fertility and K+ homeostasis: role of the renal H,K-ATPase type 2. A. Salhi, C. Lamouroux, N.B. Pestov, N.N. Modyanov, A. Doucet and G. Crambert. Pflugers Arch. (2013) 465, 1149-1158. PMID: 23440459
Renal proteinase activated receptor 2: A new actor in the control of blood pressure and plasma potassium level. L. Morla, G. Brideau, M. Fila, G. Crambert, L. Cheval, P. Houillier, S. Ramakrishnan, M. Imbert-Teboul and A. Doucet. J. Biol. Chem. (2013) 288, 10124-10131. PMID: 23430254
Circadian expression of H,K-ATPase type 2 contributes to the stability of plasma K+ levels. A. Salhi, G. Centeno, D. Firsov and G. Crambert. FASEB J. (2012) 26, 2859-2867. PMID: 22459151
Expression profile of nuclear receptors along male mouse nephron segments reveals a link between ERRβ and thick ascending limb function. H. Krid, A. Dorison A. Salhi, L. Cheval and G. Crambert. Plos ONE (2012) e34223. PMC: 3311618
Regulation of pendrin by cAMP: possible involvement in b adrenergic-dependent NaCl retention. A. Azroyan, L. Morla, G. Crambert, K. Laghmani, S. Ramakrishnan, A. Edwards and A. Doucet. Am. J. Physiol. (Renal Physiol.) (2012) 302, F1180-1187. PMID: 22262479
Chronic potassium depletion increases adrenal progesterone production which is necessary for efficient renal retention of potassium. B. Elabida, A. Edwards, A. Salhi, A. Azroyan, H. Fodstad, P. Meneton, A. Doucet, M. Bloch-Faure and G. Crambert. Kidney Int. (2011) 80, 256-262. PMID: 21326170
Edwards. Regulation of pendrin by pH: dependence on glycosylation. A. Azroyan, K. Laghmani, G. Crambert, D. Mordasini, A. Doucet and A. Biochem. J. (2011) 434, 61-72. PMID: 21073444
Membrane progestin receptors mPR : beyond the controversy, can we move forward ? A. Salhi, J. Lemale, N. Paris, M. Bloch-Faure, G. Crambert. Biomol. Concepts. (2010) 1, 41-47. ARTICLE
Mapping of sex hormone receptors and their modulators along the nephron of male and female mice. A. Grimont, M. Bloch-Faure, B. El Abida, G. Crambert. FEBS Lett. (2009) 583, 1644-1648. PMID: 19401201
Membrane progestin receptor a and g in renal epithelium. J. Lemale, M. Bloch-Faure, A. Grimont, B. Elabida, M. Imbert-Teboul and G. Crambert. BBA-Molec. Cell Res. (2008), 1783, 2234-2240. PMID: 18722485
Proteinase-activated receptor 2 stimulates Na,K-ATPase and sodium reabsorption in native kidney epithelium. L. Morla, G. Crambert, D. Mordasini, G. Favre, A. Doucet, and M. Imbert-Teboul. J. Biol. Chem. (2008), 283, 28020-28028. PMID: 18678869