Degradation of human lung elastin matrix

Jiangtao He, Shuren Ma, Jerome Cantor, Toyonobu Usuki, Georgia Dolios, Rong Wang, Gerard M. Turino, Yong Y. Lin

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Elastin matrix are significant structural constituents of skin, blood vessels, lung, and other connective tissues, where they provide physical recoil to distorting forces and contribute to normal physiological function. Degradation of elastin-containing tissues can occur in prevalent diseases resulting in complex mixtures of elastin-derived peptides, which remain largely uncharacterized due to the insoluble nature of elastin and its complex crosslinking structure. We compared proteolytic activity of several proteinases that cause degradation of human lung elastin matrix. The resulting peptides were characterized by high performance liquid chromatography and tandem mass spectrometry (LC-MS/MS), which results in the identification of several hundreds of linear peptides that belong to non-crosslinking domains of soluble elastin precursor tropoelastin. The analysis of the proteolytically cleaved sites of tropoelastin domains suggested that two alanine-rich lysine peptide chains at the domains 19 and 25 of tropoelastin are involved in the crosslink formation and it is proposed that a tetrafunctional crosslink structure is formed by condensation between the two domains, KAAAK (K at the loci 375 and 379) and KSAAK (K at the loci 529 and 533) of tropoelastin. The proposed crosslink can be chemically synthesized as a molecular model for the elastin crosslinking structure. We further compared in vitro proteolysis of a normal lung and a lung from a chronic obstructive pulmonary disease (COPD) patient. The proteolysis showed the three proteases HNE, MMP12 and PR3 are the most effective toward elastin matrix degradation, which may also occur in vivo during COPD. The proteolysis of the COPD lung produced decreased amount of desmosine/isodesmosine (DES/IDS) crosslink peptides compared to that of the normal lung but involved more proteolytic sites, which indicated significant pathological degradation of the crosslinks had occurred within the elastin matrix of the COPD lung resulting in an altered structural integrity. This finding could be a basis for progression of lung tissue breakdown once COPD is initiated and be a mechanism for clinical progression of COPD.

Original languageEnglish
Pages (from-to)105-124
Number of pages20
JournalCurrent Topics in Peptide and Protein Research
StatePublished - 2016


  • COPD
  • Crosslink structure
  • Elastin
  • Elastin peptides


Dive into the research topics of 'Degradation of human lung elastin matrix'. Together they form a unique fingerprint.

Cite this