Alain Doucet

 

Research projects:

 

Our projects are related to the normal regulation and the pathologic dysregulations of ion transport, and their consequences on body homeostasis. Our research proceeds either from function to genes or the reverse way, and associates single gene studies with omic strategies. Presently, our main focuses are on 1) the role of proteinase activated receptor 2 in the regulation of sodium and potassium transport in the distal nephron and its importance in the control of blood pressure and plasma potassium concentration, 2) the mechanism of renal sodium retention and capillary permeabilization in nephrotic syndrome and their role in edema formation, 3) the mechanism of adaptive cell proliferation during acidosis and its impact on acid-base balance, 4) the functional characterization of calcium transport defect in mouse invalidated for Msx2 gene, and 5) the identification of molecular markers of kidney carcinomas.

Medullary collecting duct from acid loaded mice (3 days) showing long files of AE1 positive (a intercalated) cells (labeled in red)
Medullary collecting duct from acid loaded mice (3 days) showing long files of AE1 positive (a intercalated) cells (labeled in red)

Team:

 Alain Doucet :  Emeritus CNRS

Lydie Cheval:    Engineer   

Luciana Morla:  Engineer                              

       

Selected publication:

 

Renal proteinase activated receptor 2: A new actor in the control of blood pressure and plasma potassium level. Morla L,  Brideau G, Fila M,  Crambert G, Cheval L, Houillier P, Ramakrishnan S, Imbert-Teboul, Doucet A. J Biol Chem 288: 10124-10131, 2013. PMID:23430254

 

Alpha-ketoglutarate regulates acid-base balance through an intra-renal paracrine mecha-nism.  Tokonami N*, Morla L*, Centevo G, Mordasini D, Ramakrishnan SK, Nikolaeva S, Wagner CA, Bonny O, Houillier P*, Doucet A*, Firsov D*. J Clin Invest 123: 3166-3171, 2013. PMID:23934124

 

WNK1-related Familial Hyperkalemic Hypertension results from an increased expression of L-WNK1 specifically in the distal nephron. Vidal-Petiot E, Elvira-Matelot E, Mutig K, Soukaseum C, Baudrie V, Wu S, Cheval L, Huc E, Cambillau M, Bachmann S, Doucet A, Jeunemaitre X, Hadchouel J. Proc Natl Acad Sci USA, 110: 14366-14371, 2013. PMID:23940364.

 

Albuminuria induces a pro-inflammatory and pro-fibrotic response in cortical collecting duct cells via the 24p3 receptor. Dizin E, Hasler U, Nlandu-Khodo S, Fila M, Roth I, Ernandez T, Doucet A, Martin PY, Feraille E*, de Seigneux S*. Am J Physiol, 305: F1053-F1063, 2013. PMID:23884139.


 Regulation of pendrin by cAMP: possible involvement inb adrenergic-dependent NaCl retention. Azroyan A, Morla L, Crambert G, Laghmani K, Ramakrishnan S, Edwards A, Doucet A. Am J Physiol,302: F1180-F1187, 2012. PMID:22262479.

 

Activation of the renal Na-Cl cotransporter by angiotensin II is a WNK4-dependent process. Castaneda-Bueno, M, Cervantes-Perez LG, Vazquez N, Uribe N, Kantesaria S, Morla L, Bobadilla NA, Doucet A, Alessi DR, Gamba G. Proc Natl Acad Sci USA, 109: 7929-7934, 2012. PMID:22550170.

 

A new methodology for quantification of alternatively spliced exons reveals a highly tissue-specific expression pattern of WNK1 isoforms. Vidal-Petiot E, Cheval L, Faugeroux J, Malard T, Doucet A, Jeunemaitre X, Hadchouel J. PlosONE, e37751, 2012. PMID:22701532.

 

Of mice and men: divergence of gene expression patterns in kidney. Cheval L, Pierrat F, Rajerison R, Piquemal D, Doucet A. PlosONE, e46876, 2012. PMID:21606114.

 

Atlas of gene expression in the mouse kidney: New features of glomerular parietal cells. Cheval L, Pierrat F, Dossat C, Genete M, Imbert-Teboul M, Duong Van Huyen JP, Poulain J, Wincker P, Weissenbach J, Piquemal D, Doucet A. Physiol Genomics 43 : 161-173, 2011. PMID:21081658.

 

Inhibition of K+ secretion in the distal nephron in the nephrotic syndrome: Possible role of albuminuria.  Fila M, Brideau G, Morla L, Cheval L, Deschênes G, Doucet A. J Physiol, 589: 3611-3621, 2011. PMID:21606114.

 

Tissue compartment analysis for biomarker discovery by gene expression profiling. Disset A, Cheval L Soutourina O, Duong Van Huyen JP, Li G, Genin C, Tostain J, Loupy A, Doucet A*, Rajerison R*. PlosONE, e7779, 2009. PMID:19901995.

 GDF15 triggers homeostatic proliferation of acid-secreting collecting duct cells. Duong Van Huyen JP, Cheval L, Bloch-Faure M, Belair MF, Heudes D, Bruneval P, Doucet A. J Am Soc Nephrol, 19: 1965-1974, 2008. PMID:18650486.

 

Proteinase-activated receptor 2 stimulates Na,K-ATPase and sodium reabsorption in native kidney epithelium.  Morla L, Crambert G, Mordasini D, Favre G, Doucet A*, Imbert-Teboul M*.  J Biol Chem. 283: 28020-28028, 2008. PMID:18678869.

 

Retention and ascites formation in a cholestatic cirrhotic mice model: Role of aldosterone and mineralocorticoid receptor ? Ackermann D, Mordasini D, Cheval L, Imbert-Teboul M, Vogt B, Doucet A. Sodium Hepatology, 46: 173-179, 2007. PMID:17596887.

 kidney collecting duct acid-base “regulon”. Cheval L, Morla L, Elalouf JM, Doucet A. The Physiol Genomics, 27: 271-281, 2006. PMID:16868073.

 

T cell transcriptome analysis points up a thymic disorder in idiopathic nephrotic syndrome.  Mansour H, Cheval L, ElaloufJM, Aude JC, Alyanakian MA, Mougenot B, Doucet A, Deschênes G. Kidney Int, 67: 2168-2177, 2005. PMID:15882260.

 

Hyperaldosteronemia and activation of the epithelial sodium channel are not required for sodium retention in puromycin-induced nephrosis.  Lourdel S, Löffing J, Favre G, Paulais M, Nissant A, Fakitzas P, Créminon C, Féraille E, Verrey F, Teulon J, Doucet A, Deschênes G. J Am Soc Nephrol, 16: 3642-3650, 2005. PMID:16267158

 

Plasticity of mouse renal collecting duct in response to potassium depletion. Cheval L, Duong Van Huyen JP, Bruneval P, Verbavatz JM, Elalouf JM, Doucet A. Physiol Genomics 19: 61-73, 2004. PMID:15238618.
 

A panoramic view of gene expression in the human kidney. Garonne-Chabardès D, Méjean A, Aude JC, Cheval L, DiStefano A, Gaillard MC, Imbert-Teboul M, Wittner M, Balian C, Anthouard V, Robert C, Ségurens B, Wincker P, Weissenbach J, Doucet A, Elalouf JM. Proc Natl Acad Sci USA 100: 13710-13715, 2003. PMID:14595018.

 

PKA-independent activation of ERK and H,K-ATPase in native kidney cells : Role of Epac I. Laroche-Joubert N, Marsy S, Michelet S, Imbert-Teboul M, Doucet A. J Biol Chem 277 : 18598-18604, 2002. PMID:11897793.

 

Collecting duct is a site of sodium retention in PAN nephrosis : a rationale for amiloride therapy. Deschênes G, Wittner M, DiStefano A, Jounier S, Doucet A. J Am Soc Nephrol 12: 598-601, 2001. PMID:11181809.

 

 

Collecting duct Na+/K+-ATPase activity is correlated with urinary sodium excretion in rat nephrotic syndromes. Deschênes G, Doucet A. J Am Soc Nephrol 11 : 604-615, 2000. PMID:10752519.