Glomerulonephritis and Focal Segmental Glomerulosclerosis as a Model to Investigate the Link between Inflammation and Kidney Disease: <br/>From Basic Mechanisms to Clinical Application

Cel

"Rapidly progressive glomerulonephritis (RPGN) and focal and segmental glomerulosclerosis (FSGS) are severe kidney diseases responsible for irreversible renal failure, which is a major risk factor for mortality. Despite the aggressiveness of immunosuppressive protocols applied, treatments against RPGN have limited effectiveness. Similarly, there is no specific treatment for FSGS. We built this research project on novel identification of molecular pathways and markers of pathogenic glomerular epithelial cells (GEC). Although major roles of endothelial activation with immune-mediated insult and imbalance between coagulation and fibrinolysis have been demonstrated, our findings reinforce this paradigm that “activation” of resident glomerular cells play a key role in disease and extend the concept by examining interactions between surrounding cellular systems. We hypothesize that abnormal activation of G-protein coupled receptors (GPCRs) and EGFR may synergize to switch the phenotype of GECs from healthy to pathological. We propose that coagulation and dysfunction of the capillary barrier, may provide GPCR ligands to receptors present in target cells such as GECs. GPCRs, themselves implicated in GN, are known to transactivate the EGFR. The EGFR has the potential to amplify actions of GPCRs in GECs, leading to cytoskeletal rearrangement, and cell death. We hypothesise that interactions between “switched GECs” and T cells are essential for the perpetuation of the immuno-inflammatory response in such glomerular diseases, after the potentially groundbreaking discovery that lymphocytes display functional EGFR, sensitive to ligands produced by pathological GECs. Finally, we will harness this knowledge for a better identification of patients at risk of glomerular demolition. Our project should identify complementary therapeutic pathways that could then be targeted on top of current immunosuppressive regiments. We also propose that this approach would be beneficial to FSGS."

Dziedzina nauki

System finansowania

ERC-SG - ERC Starting Grant

Instytucja przyjmująca

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE

Wkład UE

€ 1 364 466,00

Adres

RUE DE TOLBIAC 101
75654 Paris
Francja

Region

Ile-de-France Ile-de-France Paris

Rodzaj działalności

Research Organisations

Kontakt administracyjny

Nicolas Jeanjean (Mr.)

Kierownik naukowy

Pierre-Louis Tharaux (Dr.)

Linki

Kontakt z organizacją Strona internetowa

Koszt całkowity

Brak danych

Beneficjenci (1)