Development of the dipeptidyl peptidase 4 family and its association with lung diseases: a narrative review

Ershi Hua; Dongmei Xu; Huamao Chen; Shuwen Zhang; Jian Feng; Liqin Xu

doi:10.21037/jtd-23-1158

Development of the dipeptidyl peptidase 4 family and its association with lung diseases: a narrative review

J Thorac Dis. 2023 Dec 30;15(12):7024-7034. doi: 10.21037/jtd-23-1158. Epub 2023 Dec 12.

Authors

Ershi Hua^#^{1

2}, Dongmei Xu^#¹, Huamao Chen¹, Shuwen Zhang¹, Jian Feng¹, Liqin Xu¹

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.
² Department of Clinical Laboratory, Affiliated Nantong Hospital of Shanghai University (The Six People's Hospital of Nantong), Nantong, China.

^# Contributed equally.

Abstract

Background and objective: Dipeptidyl peptidase (DPP)4 is a member of a subfamily of serine peptidase S9. DPP4, expressed as a type II transmembrane protein, has a wide tissue distribution and is most active in the lung and small intestine. Many substrates of DPP4 have been identified, including neuropeptides, chemokines, and glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptides (GIPs). DPP4 inhibitors are clinically useful in the treatment of type 2 diabetes mellitus. DPP9, an N-terminal dipeptide targeting enzyme with proline or alanine, may have DPP4-like activity. DPP9 is ubiquitously expressed at human and rodent messenger RNA (mRNA) levels and therefore may play a role in the immune system and epithelial cells. It has been shown that DPP9 plays an important signaling role in the regulation of survival and proliferation pathways and is also involved in cell migration, apoptosis, and cell adhesion. In recent years, there has been further progress in DPP9 inhibition through activation of apoptosis by the inflammasome sensor protein Nlrp1b. This study aims to investigate the association of DPP4 family members and DPP9 with lung disease.

Methods: The literature search was initiated using the PubMed database. We searched for the content (DPP4) AND (Lung Diseases), (DPP9) AND (Lung Diseases), from which we filtered the literature we needed.

Key content and findings: Given the high biological activity of the DPP4 family, their involvement in various lung diseases is highly relevant. There is growing evidence for the importance of DPP4 and DPP9 of the DPP4 family in lung diseases, which are closely associated with diseases such as asthma, lung infections, pulmonary fibrosis (PF), and lung cancer.

Conclusions: This review summarizes most of the current evidence that DPP4/9 is associated with lung disease. Within the DPP4 family, the role of DPP4 in particular in respiratory disease is important.

Keywords: Dipeptidyl peptidase 4/9 (DPP4/9); asthma; lung cancer; pulmonary infections.

Publication types

Review