Thrombospondin-1–Deficient Mice Are Not Protected from Bleomycin-Induced Pulmonary Fibrosis

• DOI: 10.1165/rcmb.2009-0019oc
• Publication Date: 2010-06-26T00:49:57Z
• Authors: Michael E. Ezzie; Melissa G. Piper; Christine Montague; Christie A. Newland; Judy M. Opalek; Chris Baran; Naeem Ali; David Brigstock; Jack Lawler; Clay B. Marsh
• Keywords: Thrombospondin 1

Thrombospondin-1 (TSP-1) is an extracellular protein critical to normal lung homeostasis, and reported activate latent transforming growth factor-β (TGF-β). Because active TGF-β causally involved in fibrosis after bleomycin challenge, alterations TSP-1 may be relevant pulmonary fibrosis. We sought determine the effects of deficiency on susceptibility bleomycin-induced a murine model. Age-matched sex-matched C57BL/6 wild-type (WT) TSP-1-deficient mice were treated twice weekly for 4 weeks with intraperitoneal (0.035 U/g) or PBS, allowed rest 1 week before being killed. Their lungs inflated fixed formalin, paraffin-embedded, sectioned. A certified veterinary pathologist blindly scored each slide inflammation Lungs homogenized obtain RNA real-time RT-PCR analysis connective tissue factor (CTGF) collagen I, Western blotting detect phospho-Smad2, total Smad2/3, respectively. In response treatment, measures inflammation, along CTGF I mRNA concentrations, increased compared WT mice. Notably, Smad 2/3 signaling was equal strength knockout bleomycin, suggesting that not required activation TGF-β. These results demonstrate does protect from systemic associated expression CTGF.