Saturday September 25, 2021 - 15:50 to 17:05
Platelet-derived TGFβ1: Assessment of its role in liver regeneration in mice
Ana Maria Quintela Pousa1, Nemanja Cvjetan2, Alexandre Balaphas3, Jeremy Meyer3, Katrin Schäfer4, Peter Walde2, Bernhard Egger5, Leo Buhler5, Carmen Gonelle-Gispert1.
1Surgical Research Unit, Medical Surgical specialities, University of Fribourg,, Fribourg, Switzerland; 2Department of Materials, ETH Zürich, Zurich, Switzerland; 3Department of Digestive Surgery, University Hospitals Geneva, Geneva, Switzerland; 4Department of Cardiology, Cardiology I, University Medical Center Mainz, Mainz, Germany; 5General Surgery, HFR Fribourg, Fribourg, Switzerland
How platelets contribute to liver regeneration is still unclear. Recently, platelet-derived TGFβ1 has been shown to induce IL-6 secretion from liver sinusoidal endothelial cells, a factor known to be essential for liver regeneration. TGFβ1 is a multifunctional cytokine implicated in the regulation of cell growth, cell proliferation, and cell differentiation. Platelets contain high amounts of TGFβ1. The aim of the study was to investigate whether the absence of platelet-TGFβ1 affects liver regeneration in mice after 2/3 partial hepatectomy (HPx) using Cre/LoxP knockout (ko) mice deficient in platelet-TGFβ1.
Hepatocyte proliferation rate was determined by immunofluorescence staining against Ki67 on liver sections of two-third hepatectomized C57BL/6 wild-type (wt) and PF4CreTgfb1f/f (ko) mice at 0, 4, 72 and 120h after HPx. At all-time points, blood was retrieved by cardiac puncture from wt and ko mice and serum levels of latent TGFβ1 were analysed by ELISA.
Ki67 positivity showed the highest proliferative index at 72h after hepatectomy in wt (2.59-fold higher) compared to ko mice. However, no changes between groups were observed at 120h. Serum TGFβ1 concentration in wt mice decreased from 169±41ng/ml (0h) to 49±38ng/ml (4h) and increased to 82±34ng/ml at 72h, while in ko mice TGFβ1 concentration increased from 3.7±0.03ng/ml (0h) to 22±19ng/ml at 72h.
After HPx, platelet-TGFβ1 ko mice showed a significant decrease in hepatocyte proliferation at 3 days compared to wt mice. The strong variation of TGFβ1 levels in sera from wt mice after HPx suggest that platelet numbers vary strongly during liver regeneration. In ko mice, where TGFβ1 concentration is residual in platelets, serum levels of latent TGFβ1 increased between 0h and 72h suggesting an additional platelet-independent origin of TGFβ1 during liver regeneration. Overall, our findings suggest that platelet-TGFβ1 supports liver regeneration in mice and might be a promising target for therapeutic strategies to induce liver regeneration.