Distal lung microenvironment triggers release of mediators recognized as potential systemic biomarkers for idiopathic pulmonary fibrosis

Dimitrios Kalafatis, Anna Löfdahl, Per Näsman, Göran Dellgren, Åsa M. Wheelock, Linda Elowsson Rendin, Magnus Sköld, Gunilla Westergren-Thorsson

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with an unmet need of biomarkers that can aid in the diagnostic and prognostic assessment of the disease and response to treatment. In this two-part explorative proteomic study, we demonstrate how proteins associated with tissue remodeling, inflammation and chemotaxis such as MMP7, CXCL13 and CCL19 are released in response to aberrant extracellular matrix (ECM) in IPF lung. We used a novel ex vivo model where decellularized lung tissue from IPF patients and healthy donors were repopulated with healthy fibroblasts to monitor locally released mediators. Results were validated in longitudinally collected serum samples from 38 IPF patients and from 77 healthy controls. We demonstrate how proteins elevated in the ex vivo model (e.g., MMP7), and other serum proteins found elevated in IPF patients such as HGF, VEGFA, MCP-3, IL-6 and TNFRSF12A, are associated with disease severity and progression and their response to antifibrotic treatment. Our study supports the model’s applicability in studying mechanisms involved in IPF and provides additional evidence for both established and potentially new biomarkers in IPF.

Originalspråkengelska
Artikelnummer13421
TidskriftInternational Journal of Molecular Sciences
Volym22
Nummer24
DOI
StatusPublished - 2021 dec.

Ämnesklassifikation (UKÄ)

  • Cell- och molekylärbiologi
  • Lungmedicin och allergi

Fingeravtryck

Utforska forskningsämnen för ”Distal lung microenvironment triggers release of mediators recognized as potential systemic biomarkers for idiopathic pulmonary fibrosis”. Tillsammans bildar de ett unikt fingeravtryck.

Citera det här