| First Author | Ehrlich L | Year | 2018 |
| Journal | Gene Expr | Volume | 18 |
| Issue | 3 | Pages | 197-207 |
| PubMed ID | 29580318 | Mgi Jnum | J:328398 |
| Mgi Id | MGI:6881171 | Doi | 10.3727/105221618X15216453076707 |
| Citation | Ehrlich L, et al. (2018) alpha7-nAChR Knockout Mice Decreases Biliary Hyperplasia and Liver Fibrosis in Cholestatic Bile Duct-Ligated Mice. Gene Expr 18(3):197-207 |
| abstractText | alpha7-nAChR is a nicotinic acetylcholine receptor [specifically expressed on hepatic stellate cells (HSCs), Kupffer cells, and cholangiocytes] that regulates inflammation and apoptosis in the liver. Thus, targeting alpha7-nAChR may be therapeutic in biliary diseases. Bile duct ligation (BDL) was performed on wild-type (WT) and alpha7-nAChR-/- mice. We first evaluated the expression of alpha7-nAChR by immunohistochemistry (IHC) in liver sections. IHC was also performed to assess intrahepatic bile duct mass (IBDM), and Sirius Red staining was performed to quantify the amount of collagen deposition. Immunofluorescence was performed to assess colocalization of alpha7-nAChR with bile ducts (costained with CK-19) and HSCs (costained with desmin). The mRNA expression of alpha7-nAChR, Ki-67/PCNA (proliferation), fibrosis genes (TGF-beta1, fibronectin-1, Col1alpha1, and alpha-SMA), and inflammatory markers (IL-6, IL-1beta, and TNF-alpha) was measured by real-time PCR. Biliary TGF-beta1 and hepatic CD68 (Kupffer cell marker) expression was assessed using IHC. alpha7-nAChR immunoreactivity was observed in both bile ducts and HSCs and increased following BDL. alpha7-nAChR-/- BDL mice exhibited decreased (i) bile duct mass, liver fibrosis, and inflammation, and (ii) immunoreactivity of TGF-beta1 as well as expression of fibrosis genes compared to WT BDL mice. alpha7-nAChR activation triggers biliary proliferation and liver fibrosis and may be a therapeutic target in managing extrahepatic biliary obstruction. |
