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001005353 1001_ $$0P:(DE-HGF)0$$aOrtiz, Cristina$$b0
001005353 245__ $$aNeprilysin-dependent neuropeptide Y cleavage in the liver promotes fibrosis by blocking NPY-receptor 1
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001005353 520__ $$aDevelopment of liver fibrosis is paralleled by contraction of hepatic stellate cells (HSCs), the main profibrotic hepatic cells. Yet, little is known about the interplay of neprilysin (NEP) and its substrate neuropeptide Y (NPY), a potent enhancer of contraction, in liver fibrosis. We demonstrate that HSCs are the source of NEP. Importantly, NPY originates majorly from the splanchnic region and is cleaved by NEP in order to terminate contraction. Interestingly, NEP deficiency (Nep−/−) showed less fibrosis but portal hypertension upon liver injury in two different fibrosis models in mice. We demonstrate the incremental benefit of Nep−/− in addition to AT1R blocker (ARB) or ACE inhibitors for fibrosis and portal hypertension. Finally, oral administration of Entresto, a combination of ARB and NEP inhibitor, decreased hepatic fibrosis and portal pressure in mice. These results provide a mechanistic rationale for translation of NEP-AT1R-blockade in human liver fibrosis and portal hypertension.
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001005353 7001_ $$0P:(DE-HGF)0$$aKlein, Sabine$$b1
001005353 7001_ $$0P:(DE-HGF)0$$aReul, Winfried H.$$b2
001005353 7001_ $$0P:(DE-HGF)0$$aMagdaleno, Fernando$$b3
001005353 7001_ $$0P:(DE-HGF)0$$aGröschl, Stefanie$$b4
001005353 7001_ $$0P:(DE-HGF)0$$aDietrich, Peter$$b5
001005353 7001_ $$0P:(DE-HGF)0$$aSchierwagen, Robert$$b6
001005353 7001_ $$0P:(DE-HGF)0$$aUschner, Frank E.$$b7
001005353 7001_ $$00000-0002-2894-3188$$aTorres, Sandra$$b8
001005353 7001_ $$0P:(DE-HGF)0$$aHieber, Christoph$$b9
001005353 7001_ $$0P:(DE-HGF)0$$aMeier, Caroline$$b10
001005353 7001_ $$0P:(DE-HGF)0$$aKraus, Nico$$b11
001005353 7001_ $$00000-0001-9949-0975$$aTyc, Olaf$$b12
001005353 7001_ $$00000-0003-2879-7560$$aBrol, Maximilian$$b13
001005353 7001_ $$0P:(DE-HGF)0$$aZeuzem, Stefan$$b14
001005353 7001_ $$0P:(DE-HGF)0$$aWelsch, Christoph$$b15
001005353 7001_ $$0P:(DE-HGF)0$$aPoglitsch, Marco$$b16
001005353 7001_ $$0P:(DE-HGF)0$$aHellerbrand, Claus$$b17
001005353 7001_ $$0P:(DE-Juel1)169976$$aAlfonso-Prieto, Mercedes$$b18$$ufzj
001005353 7001_ $$0P:(DE-HGF)0$$aMira, Fabio$$b19
001005353 7001_ $$0P:(DE-HGF)0$$aKeller, Ulrich auf dem$$b20
001005353 7001_ $$0P:(DE-HGF)0$$aTetzner, Anja$$b21
001005353 7001_ $$0P:(DE-HGF)0$$aMoore, Andrew$$b22
001005353 7001_ $$00000-0002-6725-4473$$aWalther, Thomas$$b23
001005353 7001_ $$00000-0002-7028-3881$$aTrebicka, Jonel$$b24$$eCorresponding author
001005353 773__ $$0PERI:(DE-600)2649101-1$$a10.1016/j.celrep.2023.112059$$gVol. 42, no. 2, p. 112059 -$$n2$$p112059$$tCell reports$$v42$$x2211-1247$$y2023
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