From kidney phenotypic alterations to novel diagnostic markers and targets of therapy of chronic kid
Team 2 - Remodelling and repair of renal tissue Lab, Inserm UMRS 702
During the past years our team has contributed in the elucidation of the mechanisms of CKD by identifying several critical steps of the molecular and cellular events leading to the development of renal vascular, glomerular and tubulointerstitial fibrosis. As we are closely connected with clinical departments, and we have also contributed to the establishment of several patients' cohorts; this bench to the bedside (and vice versa) approach creates unique opportunities to advance our knowledge on clinical nephrology and public health in general.
Our basic research strategy is based either on the use of genetically modified mice to investigate the role of a pre-defined protein, or by applying therapy-driven hypotheses in standard strains to uncover the underlying mechanisms and mediators. Using the gene-targeted approach, we showed a role of Notch3 in the control of renal hemodynamics and demonstrated the importance of the balance between calpain and calpastatin in regulating renal inflammation. We also discovered that a putative collagen receptor, the DDR1, is a critical pro-inflammatory mediator, and that depletion of vitronectin and Cx43 represent novel potential therapeutic targets. Using the therapeutic approach, we demonstrated that blockade of angiotensin II action is a necessary but not sufficient therapeutic strategy, one which should be associated with additional treatments. We also characterized the renal urothelial cells, elucidating the complexity of the underlying mechanisms in every step of the evolution of renal diseases and advancing new interesting questions concerning the renal function during pathological conditions.
During the next years, we will continue expanding our previous findings by investigating calpain and DDR1 as targets of therapy. In addition, new projects emerged during the last year, and the preliminary data obtained convince us to invest more effort and time. These projects concern the role of inter-endothelial junction molecules in renal inflammatory disease, the neo-activation of Notch3 pathway as controller of renal cell plasticity, the identification of periostin as a marker of renal function and potential target for therapy. Most of these hypotheses have been patented. In parallel, we are studying the involvement of epigenetic modifications, and more specifically histone acetylation in the renal phenotype changes and development of CKD.
Fields of interest
Contact infoAddress: Inserm UMRS 1155, Bâtiment Recherche, Hôpital Tenon, 4 rue de la Chine
Postal code: 75020
Telephone: +33 1 56 01 66 53
Fax: +33 1 56 01 66 59
- Kavvadas P, Weis L, Abed A, Felman D, Dussaule JC, Chatziantoniou C.
Renin inhibition reverses renal disease in transgenic mice by shifting the balance between pro and anti-fibrotic agents
Hypertension 61, 901-907 (2013)
- Huby AC, Kavvadas P, Alfieri C, Abed A, Toubas J, Placier S, Rastaldi MP, Dussaule JC, Chatziantoniou C, Chadjichristos C.
The RenTg mice: a powerful tool to study hypertension-induced chronic kidney disease
PLoS One 7, e52362 (2012)
- Djudjaj S*, Chatziantoniou C*, Raffetseder U*, Guerrot D, Dussaule JC, Boor P, Kerroch M, Hanssen L, Brandt S, Dittrich A, Ostendorf T, Floege J, Zhu C, Lindenmeyer M, Cohen C, Mertens P
Notch-3 receptor activation drives inflammation and fibrosis following tubulointerstitial kidney injury
J Pathol 228, 286-299 (2012)
- Kerroch M, Guerrot D, Vandermeersch S, Placier S, Mesnard L, Jouanneau C, Rondeau E, Ronco P, Boffa JJ, Chatziantoniou C, Dussaule JC
Genetic inhibition of Discoidin Domain Receptor 1 protects mice against crescentic glomerulonephritis
Faseb J 26, 4079-4091 (2012)