| First Author | Kennedy L | Year | 2019 |
| Journal | FASEB J | Volume | 33 |
| Issue | 9 | Pages | 10269-10279 |
| PubMed ID | 31251081 | Mgi Jnum | J:289421 |
| Mgi Id | MGI:6435041 | Doi | 10.1096/fj.201802606R |
| Citation | Kennedy L, et al. (2019) Secretin/secretin receptor signaling mediates biliary damage and liver fibrosis in early-stage primary biliary cholangitis. FASEB J 33(9):10269-10279 |
| abstractText | Primary biliary cholangitis (PBC) primarily targets cholangiocytes and is characterized by liver fibrosis and biliary proliferation. Activation of the secretin (Sct)/secretin receptor (SR) axis, expressed only by cholangiocytes, increases biliary proliferation, liver fibrosis, and bicarbonate secretion. We evaluated the effectiveness of SR antagonist treatment for early-stage PBC. Male and female dominant-negative TGF-beta receptor II (dnTGF-betaRII) (model of PBC) and wild-type mice at 12 wk of age were treated with saline or the SR antagonist, Sec 5-27, for 1 wk. dnTGF-betaRII mice expressed features of early-stage PBC along with enhanced Sct/SR axis activation and Sct secretion. dnTGF-betaRII mice had increased biliary proliferation or senescence, inflammation, and liver fibrosis. In dnTGF-betaRII mice, there was increased microRNA-125b/TGF-beta1/TGF-beta receptor 1/VEGF-A signaling. Human early-stage PBC patients had an increase in hepatobiliary Sct and SR expression and serum Sct levels. Increased biliary Sct/SR signaling promotes biliary and hepatic damage during early-stage PBC.-Kennedy, L., Francis, H., Invernizzi, P., Venter, J., Wu, N., Carbone, M., Gershwin, M. E., Bernuzzi, F., Franchitto, A., Alvaro, D., Marzioni, M., Onori, P., Gaudio, E., Sybenga, A., Fabris, L., Meng, F., Glaser, S., Alpini, G. Secretin/secretin receptor signaling mediates biliary damage and liver fibrosis in early-stage primary biliary cholangitis. |
