المؤلفون: D'Silva, AM, Holland, S, Kariyawasam, D, Herbert, K, Barclay, P, Cairns, A, MacLennan, SC, Ryan, MM, Sampaio, H, Smith, N, Woodcock, IR, Yiu, EM, Alexander, IE, Farrar, MA

مصطلحات الفهرس: Journal Article

URL: http://hdl.handle.net/11343/301750

المؤلفون: La QT, Ren B, Logan GJ, Cunningham SC, Khandekar N, Nassif NT, O'Brien BA, Alexander IE, Simpson AM

وصف الملف: Electronic; application/pdf

URL الوصول: https://explore.openaire.eu/search/publication?articleId=od_______363::b840393d479feb7ee7f7ad4b15d76d3a
https://hdl.handle.net/10453/144252

المؤلفون: Kariyawasam, DST, Russell, JS, Wiley, V, Alexander, IE, Farrar, MA

مصطلحات الفهرس: 0604 Genetics, 1103 Clinical Sciences, text, Journal Article, Journal Article

URL: http://handle.unsw.edu.au/1959.4/unsworks_61857
https://orcid.org/0000-0002-4472-0902
https://orcid.org/0000-0002-4472-0902
Genetics in Medicine, 22, 3, 557-565

المؤلفون: LA QT, REN B, LOGAN GJ, CUNNINGHAM SC, KHANDEKAR N, NASSIF NT, O'BRIEN BA, ALEXANDER IE, SIMPSON AM

مصطلحات موضوعية: Endocrinology & Metabolism, 11 Medical and Health Sciences

URL الوصول: https://explore.openaire.eu/search/publication?articleId=od_______363::387da36941ed6e84fe2d23e10538fa98
https://hdl.handle.net/10453/142326

المؤلفون: Rajapaksha, IG, Gunarathne, LS, Asadi, K, Cunningham, SC, Sharland, A, Alexander, IE, Angus, PW, Herath, CB

مصطلحات الفهرس: text, Journal Article, JOUR

URL: http://handle.unsw.edu.au/1959.4/unsworks_72074
https://orcid.org/0000-0001-9151-8531
https://orcid.org/0000-0001-9151-8531
Rajapaksha, Indu G Gunarathne, Lakmie S Asadi, Khashayar Cunningham, Sharon C Sharland, Alexandra Alexander, Ian E Angus, Peter W Herath, Chandana B eng Hepatol Commun. 2019 Oct 10;3(12):1656-1673. doi: 10.1002/hep4.1434. eCollection 2019 Dec.There is a large unmet need for effective therapies for cholestatic disorders, including primary sclerosing cholangitis (PSC), a disease that commonly results in liver failure. Angiotensin (Ang) II of the renin Ang system (RAS) is a potent profibrotic peptide, and Ang converting enzyme 2 (ACE2) of the alternate RAS breaks down Ang II to antifibrotic peptide Ang-(1-7). In the present study, we investigated long-term effects of ACE2 delivered by an adeno-associated viral vector and short-term effects of Ang-(1-7) peptide in multiple drug-resistant gene 2-knockout (Mdr2-KO) mice. These mice develop progressive biliary fibrosis with pathologic features closely resembling those observed in PSC. A single intraperitoneal injection of ACE2 therapy markedly reduced liver injury (P < 0.05) and biliary fibrosis (P < 0.01) at both established (3-6 months of age) and advanced (7-9 months of age) disease compared to control vector-injected Mdr2-KO mice. This was accompanied by increased hepatic Ang-(1-7) levels (P < 0.05) with concomitant reduction in hepatic Ang II levels (P < 0.05) compared to controls. Moreover, Ang-(1-7) peptide infusion improved liver injury (P < 0.05) and biliary fibrosis (P < 0.0001) compared to saline-infused disease controls. The therapeutic effects of both ACE2 therapy and Ang-(1-7) infusion were associated with significant (P < 0.01) reduction in hepatic stellate cell (HSC) activation and collagen expression. While ACE2 therapy prevented the loss of epithelial characteristics of hepatocytes and/or cholangiocytes in vivo, Ang-(1-7) prevented transdifferentiation of human cholangiocytes (H69 cells) into the collagen-secreting myofibroblastic phenotype in vitro. We showed that an increased ratio of hepatic Ang-(1-7)
Hepatol Commun, 3, 12, 1656-1673

المؤلفون: Ren, B, La, QT, O'Brien, BA, Nassif, NT, Tan, Y, Gerace, D, Martiniello-Wilks, R, Torpy, F, Dane, AP, Alexander, IE, Simpson, AM

مصطلحات موضوعية: Cell Transplantation, Lentivirus, Transplantation, Heterologous, Diabetes Mellitus, Experimental, Mice, Disease Models, Animal, Diabetes Mellitus, Type 1, Liver, Insulin-Secreting Cells, Cell Transdifferentiation, Hepatocytes, Animals, Humans, Insulin, Cells, Cultured, Biotechnology

وصف الملف: application/pdf

URL الوصول: https://explore.openaire.eu/search/publication?articleId=od_______363::6ff144fa6b9e736fd760628e56c0a960
https://hdl.handle.net/10453/123671

المؤلفون: Tu, L, Wang, J-H, Barathi, VA, Prea, SM, He, Z, Lee, JH, Bender, J, King, AE, Logan, GJ, Alexander, IE, Bee, Y-S, Tai, M-H, Dusting, GJ, Bui, BV, Zhong, J, Liu, G-S

مصطلحات الفهرس: Journal Article

URL: http://hdl.handle.net/11343/306407

المؤلفون: Ren, B, La, QT, O'Brien, BA, Nassif, NT, Tan, Y, Gerace, D, Martiniello-Wilks, R, Torpy, F, Dane, AP, Alexander, IE, Simpson, AM

مصطلحات الفهرس: Conference Proceeding

URL: http://hdl.handle.net/10453/129828
http://purl.org/au-research/grants/nhmrc/513100
JOURNAL OF GENE MEDICINE
Joint 10th Annual Scientific Meeting of the Australian-Gene-and-Cell-Therapy-Society (AGCTS) and Australasian-Society-for-Stem-Cell-Research (ASSCR)
http://purl.org/au-research/grants/nhmrc/513100

المؤلفون: Ren, B, La, QT, O'Brien, BA, Nassif, NT, Tan, Y, Gerace, D, Martiniello-Wilks, R, Torpy, F, Dane, AP, Alexander, IE, Simpson, AM

مصطلحات موضوعية: Biotechnology

وصف الملف: application/pdf

URL الوصول: https://explore.openaire.eu/search/publication?articleId=od_______363::568e05ba061e6b505f5a800e764de16c
https://hdl.handle.net/10453/129828

المؤلفون: Ginn, SL, Hallwirth, CV, Liao, SHY, Teber, ET, Arthur, JW, Wu, J, Lee, HC, Tay, SS, Hu, M, Reddel, RR, McCormack, MP, Thrasher, AJ, Cavazzana, M, Alexander, SI, Alexander, IE

مصطلحات الفهرس: text, Journal Article

URL: http://handle.unsw.edu.au/1959.4/unsworks_53907
Molecular Therapy - Nucleic Acids, 6, 1-14