Opis projektu
Dodatkowe chromosomy mogą być związane z procesem naprawy nerek
W organizmie nieustannie zachodzą procesy wzrostu i naprawy, a nowe komórki powstają regularnie w toku mitozy, podczas której materiał genetyczny jest duplikowany, a komórka rozdziela się na dwie komórki potomne otrzymujące kompletną kopię każdego chromosomu. Endocykl to naturalna wersja cyklu komórkowego, kiedy to komórka powiela swój genom bez dzielenia się. Zachodzi on często u pierwotniaków, roślin i zwierząt, a jego rola w procesach naprawy tkanek u ssaków nie jest jasna. Zespół projektu ROAR bada potencjalną rolę endocykli w przywracaniu funkcji nerek po ostrej niewydolności nerek. Wiedza płynąca z projektu pozwoli również ograniczyć występowanie przewlekłej choroby nerek, następującej po ostrej niewydolności nerek.
Cel
Acute kidney injury (AKI) is a global public health concern which results in 1.7 million deaths per year. If not lethal in the acute phase, AKI is considered reversible as suggested by recovery of renal function. However, even mild AKI episodes carry substantial risk of developing subsequent chronic kidney disease (CKD). The pathophysiological basis for this phenomenon remains unclear.
Injury and death of tubular cells are recognized as the main factors in the pathogenesis of AKI and functional recovery from AKI was traditionally attributed to the regenerative capacity of tubular epithelial cells (TECs) which are believed to re-enter the cell cycle and repair the damage. Nevertheless, my preliminary data provide evidence that an endocycle-mediated response of remnant TECs may represent a critical mechanism of response to AKI.
Endocycles are cell cycle variants consisting of G and S phases alone that repeatedly proceed without cytokinesis and its role in repair of mammalian tissues is mostly unknown and totally unexplored in the kidney.
This proposal will be structured into 3 distinct objectives to address: 1. The physiologic relevance of endocycle for kidney function recovery after AKI 2. The role of endocycle in the progression of AKI to CKD; 3. The mechanism by which YAP1 drives endocycle and contributes to CKD development. To this end I will use lineage tracing techniques based on the FUCCI2aR reporter applied in different transgenic animal models of AKI, together with in vitro experiments in human primary cultures of renal tubular cells.
Collectively, the outcomes of this proposal are expected to provide an entirely novel view of the kidney’s response to AKI, to further our understanding of the processes that drive CKD following AKI, as well as to describe for the first time endocycle as a critical response mechanism to tissue injury in the mammalian kidney.
Dziedzina nauki
Program(-y)
Temat(-y)
System finansowania
MSCA-IF-EF-RI - RI – Reintegration panelKoordynator
50121 Florence
Włochy