The simple truth is seldom true and never simple

Abstract

Differentiation of hepatic stellate cells (HSCs) to extracellular matrix- and growth factor-producing cells supports liver regeneration through promotion of hepatocyte proliferation. We show that the neurotrophin receptor p75(NTR), a tumor necrosis factor receptor superfamily member expressed in HSCs after fibrotic and cirrhotic liver injury in humans, is a regulator of liver repair. In mice, depletion of p75(NTR) exacerbated liver pathology and inhibited hepatocyte proliferation in vivo. p75 (NTR-/-) HSCs failed to differentiate to myofibroblasts and did not support hepatocyte proliferation. Moreover, inhibition of p75(NTR) signaling to the small guanosine triphosphatase Rho resulted in impaired HSC differentiation. Our results identify signaling from p75(NTR) to Rho as a mechanism for the regulation of HSC differentiation to regeneration-promoting cells that support hepatocyte proliferation in the diseased liver.

Brain-derived neurotrophic factor increases expression of MnSOD in human circulating angiogenic cells

“…The complexity of function of p75 NTR is reflected in the ability of p75 NTR to activate diverse signaling pathways. Indeed, P75 NTR can activate three categories of intracellular signaling: 1) pro-apoptosis pathway including JNK pathway, 2) pro-survival pathways including NFκB, PI3K-AKT, and Ras/mitogen-activated protein kinase, and 3) pathways that modulate the cytoskeleton and cell regeneration including RhoA/Rho kinase (35). Our results demonstrated that BDNF activated NFκB and JNK pathways, but not other MAP kinases (p38 or Erk1/2) or AKT signaling.…”

Hepatic stellate cells and astrocytes

“…Ideally, one would like to be able to manipulate secretion of pro-NGF or NGF by regenerating hepatocytes may lead to ligand-induced p75 NTR -mediated activation of apoptotic pathways in HSCs. 64 Thus, p75 NTR signaling in HSCs may act in a paracrine manner to regulate liver regeneration after injury. The bioavailability of neurotrophins and the balance between pro-and mature NGF might regulate the biological function of p75 NTR in liver repair.…”