Dataset Information

Time and compartment resolved proteome profiling of the extracellular niche in lung injury and repair

ABSTRACT: The extracellular niche is a key regulator of tissue morphogenesis and repair, however, its composition is currently not well characterized. Quantitative mass spectrometry resolved the dynamics of 8366 proteins from total tissue and bronchioalveolar lavage fluid in the consecutive phases of repair upon bleomycin induced lung injury. Joint analysis of proteome and transcriptome revealed posttranscriptional events during tissue remodeling. We developed a quantitative detergent solubility profiling method (QDSP), which enabled comprehensive characterization of the extracellular matrix and its interactions with secreted proteins, and showed the drastically altered association of morphogens, such as basement membrane netrins, to the insoluble matrix upon injury. We discovered several ECM proteins, including Emilin-2 and Collagen-XXVIII, as constituents of the provisional repair matrix. Our space and time resolved proteomics identified a host of tissue repair factor candidates with potential to promote the early events of progenitor cell mobilization or late events of repair pathways including the resolution of fibrosis.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Lung

SUBMITTER: Herbert Schiller

LAB HEAD: Matthias Mann

PROVIDER: PXD001765 | Pride | 2015-07-21

REPOSITORIES: pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20130308_EXQ3_HeSc_SA_lungfibrosis_BAL_1_1.raw	Raw
	20130308_EXQ3_HeSc_SA_lungfibrosis_BAL_1_2.raw	Raw
	20130308_EXQ3_HeSc_SA_lungfibrosis_BAL_1_3.raw	Raw
	20130308_EXQ3_HeSc_SA_lungfibrosis_BAL_1_4.raw	Raw
	20130308_EXQ3_HeSc_SA_lungfibrosis_BAL_2_1.raw	Raw

Items per page:

1 - 5 of 258

Publications

Time- and compartment-resolved proteome profiling of the extracellular niche in lung injury and repair.

Schiller Herbert B HB Fernandez Isis E IE Burgstaller Gerald G Schaab Christoph C Scheltema Richard A RA Schwarzmayr Thomas T Strom Tim M TM Eickelberg Oliver O Mann Matthias M

Molecular systems biology 20150714 7

The extracellular matrix (ECM) is a key regulator of tissue morphogenesis and repair. However, its composition and architecture are not well characterized. Here, we monitor remodeling of the extracellular niche in tissue repair in the bleomycin-induced lung injury mouse model. Mass spectrometry quantified 8,366 proteins from total tissue and bronchoalveolar lavage fluid (BALF) over the course of 8 weeks, surveying tissue composition from the onset of inflammation and fibrosis to its full recover ...[more]

PMID: 26174933

Similar Datasets

Project description:Extrahepatic cholestasis leads to complex injury and repair processes that result in bile infarct formation, neutrophil infiltration, cholangiocyte and hepatocyte proliferation, extracellular matrix remodeling, and fibrosis. To identify early molecular mechanisms of injury and repair after bile duct obstruction, microarray analysis was performed on liver tissue 24 hours after bile duct ligation (BDL) or sham surgery. The most upregulated gene identified encodes plasminogen activator inhibitor 1 (PAI-1, Serpine 1), a protease inhibitor that blocks urokinase plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) activity. Because PAI-1, uPA, and tPA influence growth factor and cytokine processing as well as extracellular matrix remodeling, we evaluated the role of PAI-1 in cholestatic liver injury by comparing the injury and repair processes in wild-type (WT) and PAI-1-deficient (PAI-1-/-) mice after BDL. PAI-1-/- mice had fewer and smaller bile infarcts, less neutrophil infiltration, and higher levels of cholangiocyte and hepatocyte proliferation than WT animals after BDL. Furthermore, PAI-1-/- mice had higher levels of tPA activation and mature hepatocyte growth factor (HGF) after BDL than WT mice, suggesting that PAI-1 effects on HGF activation critically influence cholestatic liver injury. This was further supported by elevated levels of c-Met and Akt phosphorylation in PAI-1-/- mice after BDL. In conclusion, PAI-1 deficiency reduces liver injury after BDL in mice. These data suggest that inhibiting PAI-1 might attenuate liver injury in cholestatic liver diseases. Total RNA isolated using TRI Reagent (Sigma, St. Louis, MO) was purified with an RNeasy mini kit (Qiagen, Valencia, CA). Twenty micrograms cRNA was hybridized to a mouse GeneChip (U74Av2, Affymetrix, Santa Clara, CA) at the Siteman Cancer Center GeneChip facility as described by the manufacturer. Analyses used one mouse per chip. Gene expression changes were analyzed using Affymetrix MicroArray Suite 4.0 and GeneChip 3.1 Expression Analysis and Statistical Algorithms (Affymetrix). The complete methodology and full data sets for all 6 analyzed chips are available at http://bioinformatics.wustl.edu.beckerproxy.wustl.edu This study compares the injury and repair processed in wild-type mice after BDL.