The expression and activity of cathepsins D, H and K in asthmatic airways

PLoS One. 2013;8(3):e57245. doi: 10.1371/journal.pone.0057245. Epub 2013 Mar 6.

Abstract

Tumstatin is an anti-angiogenic collagen IV α3 fragment, levels of which are reduced in the airways of asthmatics. Its reduction may be due to the degradation by extracellular matrix (ECM) proteases. Cathepsins play a role in ECM remodelling, with cathepsin D, H and K (CTSD, CTSH and CTSK) being associated with lung diseases. CTSD modulates the NC1 domains of collagen molecules including tumstatin, while CTSH and CTSK are involved in ECM degradation. The role of these cathepsins in the regulation of tumstatin in the lung has not previously been examined. We demonstrated that CTSB, D, F, H, K, L and S mRNA was expressed in the airways. Quantification of immunohistochemistry showed that there is no difference in the global expression of CTSD, CTSH and CTSK between asthmatics and non-asthmatics. CTSD and CTSK, but not CTSH had the capacity to degrade tumstatin. No difference was observed in the activity of CTSD and H in bronchoalveolar lavage fluid of asthmatic and non-asthmatics, while CTSK was undetectable. This indicates that while CTSD possesses the potential to directly regulate tumstatin, and thus angiogenesis through this mechanism however, it is not likely to be involved in the dysregulation of tumstatin found in asthmatic airways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asthma / enzymology*
  • Asthma / genetics
  • Asthma / pathology*
  • Autoantigens / metabolism
  • Bronchoalveolar Lavage Fluid
  • Cathepsin D / genetics
  • Cathepsin D / metabolism
  • Cathepsin H / genetics
  • Cathepsin H / metabolism
  • Cathepsin K / genetics
  • Cathepsin K / metabolism
  • Cathepsins / genetics
  • Cathepsins / metabolism*
  • Collagen Type IV / metabolism
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Immunoblotting
  • Lung / enzymology*
  • Lung / pathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Autoantigens
  • Collagen Type IV
  • RNA, Messenger
  • Recombinant Proteins
  • type IV collagen alpha3 chain
  • Cathepsins
  • Cathepsin H
  • Cathepsin K
  • Cathepsin D

Grant support

This work was supported by the National Health and Medical Research Council, Australia (Grant # 570867). J.K. Burgess is supported by a NHMRC Career Development Fellowship #1032695 A. Faiz is supported by a Australian Postgraduate Award (APA) L. Harkness is supported by an Asthma Foundation of NSW Scholarship J.L. Black is supported by a NHMRC senior Principal Research Fellowship #571098 B.G.G. Oliver is supported by a NHMRC Career Development Fellowship #1026880. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.