The emerging role of dipeptidyl-peptidase-4 as a therapeutic target in lung disease

ABSTRACT

Introduction: Dipeptidyl-peptidase-4 (DPP-4) is a surface bound ectopeptidase that is commonly known as CD26 or adenosine deaminase binding protein. DPP-4 is membrane anchored but it can be cleaved by numerous proteases including matrix-metalloproteinases (MMPs). DPP-4 is expressed by endothelial and epithelial cells, the kidney, intestine and cells of the immune system; it has a broad spectrum of biological functions in immune regulation, cancer biology and glucose metabolism.

Areas covered: This article sheds light on the functions of DPP-4, the molecular mechanisms that govern its expression, it’s role in the pathogenesis of common respiratory illnesses and potential as a therapeutic target.

Expert opinion: DPP-4 has a deleterious role in respiratory disease. Its biological functions, key molecular pathways, interactions and associations are slowly being elucidated. Progressing our knowledge of the role of this multi-faceted molecule may yield vital and novel therapies for respiratory diseases such as lung cancer, asthma, and chronic obstructive pulmonary disease (COPD).

KEYWORDS:

• Asthma
• chronic obstructive pulmonary disease (COPD)
• cluster of differentiation 26 (CD26)
• dipeptidyl-peptidase-4 (DPP-4)

Article highlights

• DPP-4 can regulate the immune response, particularly with respect to T-cell activation and homeostasis by modulating chemotaxis.

• DPP-4 inhibition alleviates arterial remodeling in experimental pulmonary hypertension via inhibition of pulmonary arterial smooth muscle cell proliferation and migration.

• DPP-4 is also implicated in the pathophysiology of asthma and strongly associates with COPD due to its role in immune function.

• DPP-4 inhibition showed improved overall survival in lung cancer patients by acting on tumor immunoregulation.

• Biopharmacological inhibition of DPP-4, with the use of antibodies, DNA vaccines and small interfering RNA, is emerging as a promising novel therapeutic target in respiratory diseases and cancer.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.