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ADAM33 interactions with proteins associated with asthma

A disintegrin and metalloprotease-33 gene had novel interactions with proteins that were associated with asthma and bronchial hyperresponsiveness, according to study results.

The study’s purpose was to “identify the pathways and processes critical to asthma by assessing the functional and regulatory roles of several proteins interacting with [a disintegrin and metalloprotease-33] ADAM33 and to construct interaction networks among those genes and their products to discern the complex effect of genes involved in the manifestation of asthma,” researchers in India wrote.

The researchers identified interacting candidates of ADAM33 by using Ingenuity Pathway Analysis (IPA) and GeneMANIA tools and a literature search. Enrichment analysis of the proteins identified were conducted through the GEneSeT AnaLysis Toolkit.

Proteins including amyloid beta (A4) precursor protein, antaxin-7, alpha₄-integrin, alpha₅-integrin, alpha₉-integrin, tissue inhibitor of metalloproteinase-4, and ubiquilin-4, which had not been previously associated with asthma, interacted with ADAM33.

Seventeen protein-protein interactions and 52 mature miRNA interactions were shown through ADAM33 analysis. The toolkit, based on biological process, molecular function and cellular component, categorized 17 genes involved in ADAM33 protein-interaction network, with 12 genes involved in system development.

Several identified targets were accountable for asthma phenotypes relating to airway wall thickening, edema, inflammatory cell infiltration, connective tissue deposition, subepithelial fibrosis, myofibroblast hyperplasia, mucus metaplasia and epithelial hypertrophy.

“The proteins identified in this study were enriched for various mechanisms that are involved in airway hyperresponsiveness, and through the interaction with ADAM33, they may have potential relevance in asthma,” the researchers concluded.

Disclosure: Two researchers served as investigators for the Indian Council of Medical Research.