Figure 8.

Proteomic systems biology view of tissue remodeling upon injury and repair and protein compartmentalization in the lung

Tissue repair upon injury involves drastic remodeling of the proteome and the reactivation of developmental programs. Using state of the art quantitative mass spectrometry, we quantified more than 8,000 proteins and resolved their association with cell and tissue compartments as well as their relative abundance in the inflammation, fibrosis, remodeling, and resolution phases of tissue repair: (i) The tissue proteome data reflected the dynamics of biological processes and the transcriptional networks driving them and determined the relative proportions of various cell lineages along the tissue repair progression timeline; (ii) in-depth proteomic analysis of BALF and whole tissue discriminated true components of epithelial lining fluid from tissue leakage proteins and untangled the temporal regulation of in vivo protein secretion and receptor ectodomain shedding. This highlighted a multitude of unexpected proteins in ELF that may have important autocrine and paracrine functions in the different phases of lung repair and lung homeostasis; and (iii) our solubility profiling method (QDSP) enabled unbiased analysis of protein interactions in the ECM in vivo and quantified gain and loss of protein interactions within the ECM upon bleomycin-induced injury.