Figure 1.
NPY levels correlate with liver disease in mice and in human hepatic cirrhosis
(A) Serum NPY ELISA from control and cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) treatment, n = 7 (TIPS-group, cirrhotic patients) and n = 6 (controls), ∗∗p < 0.02 for cirrhotic patients vs. healthy individuals (absolute values).
(B) Serum NPY ELISA in cirrhotic patients shows increased NPY in Child-Pugh class C compared with Child-Pugh class A patients, n = 5 per group, ∗p < 0.05 for Child-Pugh class C vs. Child-Pugh class A cirrhotic patients. Results are expressed as mean ± standard error of the mean (SEM).
(C) Serum NPY ELISA from portal vein (PV, hepatic inflow) and hepatic vein (HV, hepatic outflow) in TIPS patients, n = 16 per group, ∗∗p < 0.02 for PV vs. HV.
(D) Serum NPY ELISA from hepatic vein (HV) and hepatic artery (HA) in n = 21 per group, n.s. (not significant).
(E) NPY levels compared with portal vein and hepatic artery, ∗∗∗p < 0.001.
(F) In silico analysis of hepatic mRNA NPY levels compared with TGFB1 expression in human liver tissues.
(G) Hepatic Nep and Col1A1 mRNA expression in patients with chronic liver disease; number of XY pairs = 17, r = 0.7472, p = 0.0006.
(H and I) Hepatic Nep mRNA expression from bile duct ligation (BDL)-treated and CCl4-treated WT (C57BL/6) mice for 2 and 4 weeks, respectively, ∗∗p < 0.02 for BDL- or CCl4-treated vs. corresponding control mice. Data were normalized to the expression of 18S RNA.
(J) Liver homogenates NPY ELISA from WT and Nep−/− mice, control vs. CCl4, ∗p < 0.05.
(K) Morphometric analysis of Sirius red staining of livers from WT mice compared with Nep−/− with and without NPYFL (left panel) and WT BDL mice vs. Nep−/− BDL with and without NPYFL (right panel). n = 5 per group, ∗∗p < 0.01, ∗∗∗p < 0.001, and n.s. (non-significant).
(L) Liver sections stain with Sirius red. Scale bar: 200 μm.
(M) Col1A1 mRNA expression of WT mice comparing non-treated controls vs. animals that were injected with full-length NPY, ∗∗p < 0.01. Col1A1 mRNA expression of Nep−/− mice after profibrotic stimuli (BDL) comparing control vs. Nep−/− after injecting full-length NPY, ∗∗p < 0.01. Data were normalized to the expression of 18S RNA.