The expression of proline-specific enzymes in the human lung

Abstract

The pathophysiology of lung diseases is very complex and proteolytic enzymes may play a role or could be used as biomarkers. In this review, the literature was searched to make an overview of what is known on the expression of the proline-specific peptidases dipeptidyl peptidase (DPP) 4, 8, 9, prolyl oligopeptidase (PREP) and fibroblast activation protein α (FAP) in the healthy and diseased lung. Search terms included asthma, chronic obstructive pulmonary disease (COPD), lung cancer, fibrosis, ischemia reperfusion injury and pneumonia. Knowledge on the loss or gain of protein expression and activity during disease might tie these enzymes to certain cell types, substrates or interaction partners that are involved in the pathophysiology of the disease, ultimately leading to the elucidation of their functional roles and a potential therapeutic target. Most data could be found on DPP4, while the other enzymes are less explored. Published data however often appear to be conflicting, the applied methods divers and the specificity of the assays used questionable. In conclusion, information on the expression of the proline-specific peptidases in the healthy and diseased lung is lacking, begging for further well-designed research.

The Counter Regulatory Axis of the Lung Renin-Angiotensin System in Severe COVID-19: Pathophysiology and Clinical Implications

“…Prolyloligopeptidase is an oligopeptidase with endopeptidase activity. It has been shown to be localised in the cytoplasm but given its ability to inactivate several neuropeptides in vitro by limited proteolysis, its involvement in the in vivo generation of immunoactive peptides and its presence in plasma it most likely also has an extracellular role [ 8 , 16 ]. Membrane-bound POP has also been described [ 17 ].…”

“…It has been widely accepted that a counter-regulatory renin-angiotensin system (RAS) axis including angiotensin (ANG)-converting enzyme 2 (ACE2)/ANG [1-7]/Mas protects the lungs from acute lung injury. However, recent evidence suggests that ACE2 expression is significantly lower in the lungs compared with other organs and tissues [ 7 ] and that generation of the protective ANG [1-7] is predominantly mediated by prolyloligopeptidase (POP), which has repeatedly been demonstrated to be involved in human pathology [ 8 ].…”

DPP4 inhibition by sitagliptin attenuates LPS-induced lung injury in mice

“…In healthy human lungs, CD26/DPP4 is expressed principally on type I and II alveolar cells, alveolar macrophages, vascular endothelium, and the pleural mesothelium (28). In addition, prior studies have suggested a functional role for CD26/DPP4 in several pulmonary diseases, such as asthma, chronic obstructive pulmonary disease, lung cancer, fibrosis, ischemia-reperfusion injury, and pneumonia (42).…”

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

“…Comorbidities are frequent in COPD and may significantly affect quality of life, escalation of symptoms, and ultimately the survival [15,16]. The pathology of COPD is yet to be fully elucidated however, a dysregulated chronic immune response is thought to be an important driver [38]. DPP-4 modulates the immune response, as previously discussed.…”