4.7 Review

Defining the versican interactome in lung health and disease

Journal

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 323, Issue 2, Pages C249-C276

Publisher

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00162.2022

Keywords

extracellular matrix; microenvironments; versican interactome

Funding

  1. National Institute of Allergy and Infectious Diseases [1R01AI136468-01, 1R01AI130280, R21AI147536, R01AI136468]
  2. University of Washington RDP [SINGH19R0]
  3. National Heart, Lung, and Blood Institute [K08HL135266, R01HL122895]

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The extracellular matrix plays a critical role in cellular processes in the lungs, with the proteoglycan versican being a key regulator in lung diseases. However, the mechanisms of how versican interacts with its binding partners and forms contextual extracellular matrices are still not fully understood.
The extracellular matrix (ECM) imparts critical mechanical and biochemical information to cells in the lungs. Proteoglycans are essential constituents of the ECM and play a crucial role in controlling numerous biological processes, including regulating cellular phenotype and function. Versican, a chondroitin sulfate proteoglycan required for embryonic development, is almost absent from mature, healthy lungs and is reexpressed and accumulates in acute and chronic lung disease. Studies using genetically engineered mice show that the versican-enriched matrix can be pro- or anti-inflammatory depending on the cellular source or disease process studied. The mechanisms whereby versican develops a contextual ECM remain largely unknown. The primary goal of this review is to provide an overview of the interaction of versican with its many binding partners, the versican interactome, and how through these interactions, versican is an integrator of complex extracellular information. Hopefully, the information provided in this review will be used to develop future studies to determine how versican and its binding partners can develop contextual ECMs that control select biological processes. Although this review focuses on versican and the lungs, what is described can be extended to other proteoglycans, tissues, and organs.

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