Date: Monday, June 13, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
Ischemia/reperfusion (I/R) is an important cause of acute renal failure and delayed graft function, and it may induce chronic renal damage by activating epithelial to mesenchymal transition (EMT) of renal tubular cells. In this contest, Heparanase (HPSE), an endonucleases that regulates FGF2- and TGFB-induced EMT, may have an important role. Therefore, aim of this study was to evaluate its role in the I/R-induced renal pro-fibrotic machinery by employing in-vitro and in-vivo models.
Wild type (wt) and HPSE-silenced renal tubular cells were subjected to hypoxia and reoxygenation in the presence or absence of SST0001, an inhibitor of HPSE. In vivo, I/R injury was induced by bilateral clamping of renal arteries for 30 min in transgenic mice over-expressing HPSE (HPA-tg) and in their wt littermates. Mice were sacrificed 48 and 72 h after I/R. Gene and protein EMT markers (α-SMA, VIM, FN and TGF-β) were evaluated by bio-molecular and histological methodologies.
In vitro: hypoxia/reoxygenation (H/R) significantly increased the expression of EMT-markers in wt, but not in HPSE-silenced tubular cells. Notably, EMT was prevented in wt cells by SST0001 treatment. In vivo: I/R induced a profound acute renal tubular necrosis and a remarkable up-regulation of EMT markers in HPA-tg mice after 48-72 h. Noteworthy, these effects were absent in wt animals.
In conclusion, our results add new insights towards understanding the renal biological mechanisms activated by I/R and they demonstrate, for the first time, that HPSE is a pivotal factor involved in the onset and development of I/R-induced EMT. It is plausible that in future the inhibition of this endoglycosidase may represent a new therapeutic approach to minimize/prevent fibrosis and slow down chronic renal disease progression in transplanted kidneys.
CITATION INFORMATION: Zaza G, Masola V, Gambaro G, Onisto M, Bellin G, Vlodavsky I, Abassi Z, Lupo A. Heparanase: A New Factor Involved in the Pro-Fibrotic Renal Biological Machinery Activated by the Ischemia/Reperfusion (I/R) Injury. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Zaza G, Masola V, Gambaro G, Onisto M, Bellin G, Vlodavsky I, Abassi Z, Lupo A. Heparanase: A New Factor Involved in the Pro-Fibrotic Renal Biological Machinery Activated by the Ischemia/Reperfusion (I/R) Injury. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/heparanase-a-new-factor-involved-in-the-pro-fibrotic-renal-biological-machinery-activated-by-the-ischemiareperfusion-ir-injury/. Accessed March 8, 2021.
« Back to 2016 American Transplant Congress