An Essential Role for Resident Fibroblasts in Experimental Lung Fibrosis Is Defined by Lineage-Specific Deletion of High-Affinity Type II Transforming Growth Factor β Receptor

Rationale: Fibrotic response to lung injury depends on development of a fibrogenic population of myofibroblasts. The importance of resident interstitial fibroblasts and role of transforming growth factor β (TGFβ) in this process is unclear.Objectives: To define the importance of TGFβ signaling in resident lung fibroblasts in the development of experimental pulmonary fibrosis.Methods: A compound genetic strategy in which mice homozygous for a floxed high-affinity type II TGFβ receptor (TβRII) allele were crossed with a transgenic strain harboring a fibroblast-specific transgene encoding ligand-dependent Cre-recombinase was used. TβRII was deleted by postnatal administration of tamoxifen over 5 days to compound mutant mice with appropriate littermate controls. Illumina microarray gene profiling and quantitative reverse transcriptase–polymerase chain reaction were used to confirm anergy to TGFβ in explanted lung fibroblasts. Bleomycin lung injury was used to induce lung fibrosis, which was analyzed by histol...