Fibrosis: In vitro fibrosis drug validation
In the case of idiopathic pulmonary fibrosis, median survival is between 2 and 7 years. The approved anti-fibrotic Nintedanib and and Pirfenidone show promise however there is still a desperate need for new treatments. Celentyx scientists have worked in the area of scarring and fibrosis and using standard readouts of fibrosis such as Smad3 signalling, extracellular matrix accumulation1,2 and collagen gel contraction3. Assays may be suitable for evaluating the impact of modulators of CTGF, FGFR1, integrins, IL-6, LOXL, p38 MAPK, PI3K, TGFb. In addition, Celentyx scientists share strong links with experts in liver fibrosis, corneal scarring and burns at the University of Birmingham. Please contact us for further information. |
Quantification of fibrotic end-points by high-content imaging
• Thickness and overlap between matrix components can also be analysed.
• Fibroblasts stimulated with TGFbeta and stained for alphaSMA.
• Confocal Z-stacks from multiple fields of view from 96-well plates acquired and analyzed.
Fibrosis publications from Celentyx Scientists
1. An immunofluorescence assay for extracellular matrix components highlights the role of epithelial cells in producing a stable, fibrillar extracellular matrix. Qureshi OS, Bon H, Twomey B, Holdsworth G, Ford K, Bergin M, Huang L, Muzylak M, Healy LJ, Hurdowar V, Johnson TS. BiolOpen. 2017 Oct 15;6(10):1423-1433. doi: 10.1242/bio.025866. http://bio.biologists.org/content/6/10/1423 bio.biologists.org/content/6/10/1423
2. Quantitative and organisational changes in mature extracellular matrix revealed through high-content imaging of total protein fluorescently stained in situ. Holdsworth G, Bon H, Bergin M, Qureshi O, PaveleyR, Atkinson J, Huang L, Tewari R, Twomey B, Johnson T. Sci Rep. 2017 Aug 30;7(1):9963. doi: 10.1038/s41598-017-10298-x. www.nature.com/articles/s41598-017-10298-x
3. No evidence for altered intracellular calcium-handling in airway smooth muscle cells from human subjects with asthma. Sweeney D*, Hollins F*,Gomez E, Mistry R, Saunders R, Alfred R, ChallissJ, and Christopher BrightlingCE. BMC Pulmonary Medicine 2015; 15: 12. https://bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-015-0009-z