Journal
PULMONARY PHARMACOLOGY & THERAPEUTICS
Volume 55, Issue -, Pages 75-83Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pupt.2019.02.005
Keywords
Precision-cut lung slices; Idiopathic pulmonary fibrosis; Bleomycin; In vitro model; Compounds testing
Categories
Ask authors/readers for more resources
Idiopathic pulmonary fibrosis (IPF) is a complex lung disease with incompletely understood pathophysiology. Effectiveness of available medicines is limited and the need for new and improved therapies remains Due to complexity of the disease, it is difficult to develop predictable in vitro models. In this study we have described precision-cut lung slices (PCLS) prepared from bleomycin treated mice as an in vitro model for testing of novel compounds with antifibrotic activity. We have shown that PCLS during in vitro incubation retain characteristics of bleomycin model with increased expression of fibrosis related genes ACTA2 (alpha-smooth muscle actin), COL1A1 (collagen 1), FN1 (fibronectin 1), MMP12 (matrix metalloproteinase 12) and TIMP1 (tissue inhibitor of metalloproteinases). To further evaluate PCLS as an in vitro model, we have tested ALK5 inhibitor SB525334 which was previously shown to attenuate fibrosis in in vivo bleomycin model and nintedanib which is the FDA approved treatment for IPF. SB525334 and nintedanib inhibited expression of fibrosis related genes in PCLS from bleomycin treated mice. In addition, comparable activity profile of SB525334 was achieved in PCLS and in vivo model. Altogether these results suggest that PCLS may be a suitable in vitro model for compound testing during drug development process.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available