In search of a small molecule agonist of the relaxin receptor RXFP1 for the treatment of liver fibrosis

Autor: Sapna Desai, Danuta Ewa Irena Mossakowska, Scott P. Webster, Duncan S. Holmes, Andrew McBride, Jonathan A. Fallowfield, Kate Simpson, Martin P. Ruediger, Mark J. Bamford, Rebecca L. Aucott, Jeremy Griggs, John P. Iredale, Ivan Caballero-Hernandez, Anna M. Hoy, Theresa J. Pell

Publikováno v: McBride, A, Hoy, A M, Bamford, M J, Mossakowska, D E, Ruediger, M P, Griggs, J, Desai, S, Simpson, K, Caballero-Hernandez, I, Iredale, J P, Pell, T, Aucott, R L, Holmes, D S, Webster, S P & Fallowfield, J A 2017, ' In search of a small molecule agonist of the relaxin receptor RXFP1 for the treatment of liver fibrosis ', Scientific Reports, vol. 7, no. 1, pp. 10806 . https://doi.org/10.1038/s41598-017-10521-9
Scientific Reports
Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid
Consejería de Sanidad de la Comunidad de Madrid
Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)

The peptide hormone human relaxin-2 (H2-RLX) has emerged as a potential therapy for cardiovascular and fibrotic diseases, but its short in vivo half-life is an obstacle to long-term administration. The discovery of ML290 demonstrated that it is possi

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b93d6cf3a5230ceb0c3d399fec3919ef
https://doi.org/10.1038/s41598-017-10521-9

Serelaxin as a potential treatment for renal dysfunction in cirrhosis: Preclinical evaluation and results of a randomized phase 2 trial

Autor: Victoria K, Snowdon, Neil J, Lachlan, Anna M, Hoy, Patrick W F, Hadoke, Scott I, Semple, Dilip, Patel, Will, Mungall, Timothy J, Kendall, Adrian, Thomson, Ross J, Lennen, Maurits A, Jansen, Carmel M, Moran, Antonella, Pellicoro, Prakash, Ramachandran, Isaac, Shaw, Rebecca L, Aucott, Thomas, Severin, Rajnish, Saini, Judy, Pak, Denise, Yates, Neelesh, Dongre, Jeremy S, Duffield, David J, Webb, John P, Iredale, Peter C, Hayes, Jonathan A, Fallowfield

Publikováno v: Snowdon, V K, Lachlan, N J, Hoy, A M, Hadoke, P W F, Semple, S I, Patel, D, Mungall, W, Kendall, T J, Thomson, A, Lennen, R J, Jansen, M A, Moran, C M, Pellicoro, A, Ramachandran, P, Shaw, I, Aucott, R L, Severin, T, Saini, R, Pak, J, Yates, D, Dongre, N, Duffield, J S, Webb, D J, Iredale, J P, Hayes, P C, Fallowfield, J A & Taal, M W (ed.) 2017, ' Serelaxin as a potential treatment for renal dysfunction in cirrhosis: Preclinical evaluation and results of a randomized phase 2 trial ', PLoS Medicine, vol. 14, no. 2, e1002248 . https://doi.org/10.1371/journal.pmed.1002248
PLoS Medicine, Vol 14, Iss 2, p e1002248 (2017)
PLoS Medicine

Background Chronic liver scarring from any cause leads to cirrhosis, portal hypertension, and a progressive decline in renal blood flow and renal function. Extreme renal vasoconstriction characterizes hepatorenal syndrome, a functional and potentiall

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::fd7aad772f0e5442da544546fa762fb9
https://www.pure.ed.ac.uk/ws/files/31790312/journal.pmed.1002248.pdf

11Beta-hydroxysteroid dehydrogenase-1 deficiency or inhibition enhances hepatic myofibroblast activation in murine liver fibrosis

Autor: Xiantong, Zou, Prakash, Ramachandran, Timothy J, Kendall, Antonella, Pellicoro, Elena, Dora, Rebecca L, Aucott, Kajal, Manwani, Tak Yung, Man, Karen E, Chapman, Neil C, Henderson, Stuart J, Forbes, Scott P, Webster, John P, Iredale, Brian R, Walker, Zoi, Michailidou

Publikováno v: Hepatology (Baltimore, Md.). 67(6)

A hallmark of chronic liver injury is fibrosis, with accumulation of extracellular matrix orchestrated by activated hepatic stellate cells (HSCs). Glucocorticoids limit HSC activation in vitro, and tissue glucocorticoid levels are amplified by 11beta

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=pmid________::67ff7599f1fa01bbf8850a7c723481c7
https://pubmed.ncbi.nlm.nih.gov/29251794

Matrix stiffness modulates proliferation, chemotherapeutic response, and dormancy in hepatocellular carcinoma cells

Autor: Rebecca G. Wells, Daniel Benten, Shaun V. Walsh, John P. Iredale, Joerg Schrader, Marielle Van Deemter, Stuart J. Forbes, Alexander Quaas, Timothy T. Gordon-Walker, Rebecca L. Aucott

Publikováno v: Schrader, J, Gordon-Walker, T T, Aucott, R L, van Deemter, M, Quaas, A, Walsh, S, Benten, D, Forbes, S J, Wells, R G & Iredale, J P 2011, ' Matrix Stiffness Modulates Proliferation, Chemotherapeutic Response, and Dormancy in Hepatocellular Carcinoma Cells ', Hepatology, vol. 53, no. 4, pp. 1192-1205 . https://doi.org/10.1002/hep.24108

There is increasing evidence that the physical environment is a critical mediator of tumor behavior. Hepatocellular carcinoma (HCC) develops within an altered biomechanical environment, and increasing matrix stiffness is a strong predictor of HCC dev

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fd702e7c3f706baaeb79d17ddae71150
https://doi.org/10.1002/hep.24108

p75 neurotrophin receptor signaling regulates hepatic myofibroblast proliferation and apoptosis in recovery from rodent liver fibrosis

Autor: Rebecca L. Aucott, John P. Iredale, Selina Hennedige, Stephen N. Hartland, R. Christopher Benyon, Madeleine A. Vernon, Timothy J. Kendall

Publikováno v: Hepatology. 49:901-910

Hepatic myofibroblast apoptosis is critical to resolution of liver fibrosis. We show that human hepatic myofibroblasts co-express p75NTR (p75 neurotrophin receptor) and sortilin, thus facilitating differential responses to mature and pro nerve growth

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a0c6211a8bebc2145194323e2cdecad1
https://doi.org/10.1002/hep.22701