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Max Planck Team Profiles Proteomics of Lung Injury and Repair

NEW YORK (GenomeWeb News) – Using label-free quantitative mass spec, a team led by Max Planck Institute researcher Matthias Mann has characterized the proteomics underlying the process of lung injury and repair.

Detailed in a paper published last week in Molecular Systems Biology, the study quantified more than 8,000 proteins from lung tissue and bronchoalveolar lavage fluid over a time period of eight weeks, following proteomic changes beginning with the start of inflammation and fibrosis through to recovery.

Notably, the researchers developed workflows that let them profile various components of the lung separately, allowing them to better investigate the interactions of these different compartments.

The approach, which they termed quantitative detergent solubility profiling (QDSP), leveraged the different relative solubilities of various lung tissue components to distinguish between them by extracting portions for analysis using increasingly more stringent detergents. They then analyzed these fractions separately using LC-MS/MS on a Thermo Fisher Q Exactive instrument, comparing protein levels in four different solubility fractions at four different time points (inflammation, day three; fibrogenesis, day 14; remodeling, day 28; and resolution, day 54) representing the injury and repair process.

In this way, they were able to investigate not only changes in protein expression during injury repair but also changes in protein localization and associations. For instance, at 14 days after injury, they identified 1,125 proteins with significantly regulated expression and 283 proteins with altered solubility profiles, suggesting changes in their localization and interactions. In all, 3,032 of the proteins measured changed significantly at at least one of the time points measured.

Among the group's findings was the novel identification of the proteins Emilin-2 and collagen-XXVIII as components of the provisional extracellular repair matrix, which plays a key role in managing processes related to injury recovery. Despite being identified in the MSB study as among the most highly regulated proteins, they had never before "been described in the context of tissue repair or fibrosis," the authors wrote.

Additionally, they were able to identify changes in the collection of secreted proteins associated with the extracellular matrix, with their QDSP-based proteomic profile both confirming previous reports of various secreted proteins interacting with the ECM and providing data for new research and validation, they said.

The work also points toward potential clinical applications, the researchers said. Specifically, they noted, the study suggests that their mass spec workflow could be applied to the analysis of bronchoalveolar lavage fluid (BALF), which is commonly monitored in patients with chronic lung disease.

"The highly streamlined nature of our LC-MS-based proteomic workflow makes the clinical translation of BALF proteomics an attractive direction for both patient stratification and drug target discovery," they wrote.

More generally, they said, the study provides a large collection of novel targets and hypotheses for follow-up as well as sample prep and mass spec methodologies for further analysis both of injury repair processes both in lung and, potentially, a variety of other tissues.