Cristina Ortiz, Sabine Klein, Winfried H Reul, Fernando Magdaleno, Stefanie Gröschl, Peter Dietrich, Robert Schierwagen, Frank E Uschner, Sandra Torres, Christoph Hieber, Caroline Meier, Nico Kraus, Olaf Tyc, Maximilian Brol, Stefan Zeuzem, Christoph Welsch, Marco Poglitsch, Claus Hellerbrand, Mercedes Alfonso-Prieto, Fabio Mira, Ulrich Auf dem Keller, Anja Tetzner, Andrew Moore, Thomas Walther, Jonel Trebicka
Development of liver fibrosis is paralleled by contraction of hepatic stellate cells (HSCs), the main profibrotic hepatic cells. Yet, little is known about the interplay of neprilysin (NEP) and its substrate neuropeptide Y (NPY), a potent enhancer of contraction, in liver fibrosis. We demonstrate that HSCs are the source of NEP. Importantly, NPY originates majorly from the splanchnic region and is cleaved by NEP in order to terminate contraction. Interestingly, NEP deficiency (Nep-/- ) showed less fibrosis but portal hypertension upon liver injury in two different fibrosis models in mice...
January 31, 2023: Cell Reports