Dipeptidyl peptidase 4 expression is not associated with an activated fibroblast phenotype in idiopathic pulmonary fibrosis

Måns Kadefors; Frida Berlin; Marie Wildt; Göran Dellgren; Sara Rolandsson Enes; Anders Aspberg; Gunilla Westergren-Thorsson

doi:10.3389/fphar.2022.953771

Dipeptidyl peptidase 4 expression is not associated with an activated fibroblast phenotype in idiopathic pulmonary fibrosis

Front Pharmacol. 2022 Aug 31:13:953771. doi: 10.3389/fphar.2022.953771. eCollection 2022.

Authors

Måns Kadefors¹, Frida Berlin¹, Marie Wildt², Göran Dellgren³, Sara Rolandsson Enes¹, Anders Aspberg², Gunilla Westergren-Thorsson¹

Affiliations

¹ Department of Experimental Medical Science, Lund University, Lund, Sweden.
² Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
³ Transplant Institute and Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.

Abstract

Dipeptidyl peptidase 4 (DPP4) has been proposed as a marker for activated fibroblasts in fibrotic disease. We aimed to investigate whether a profibrotic DPP4 phenotype is present in lung tissue from patients with idiopathic pulmonary fibrosis (IPF). The presence of DPP4⁺ fibroblasts in normal and IPF lung tissue was investigated using flow cytometry and immunohistology. In addition, the involvement of DPP4 in fibroblast activation was examined in vitro, using CRISPR/Cas9 mediated genetic inactivation to generate primary DPP4 knockout lung fibroblasts. We observed a reduced frequency of primary DPP4⁺ fibroblasts in IPF tissue using flow cytometry, and an absence of DPP4⁺ fibroblasts in pathohistological features of IPF. The in vivo observations were supported by results in vitro showing a decreased expression of DPP4 on normal and IPF fibroblasts after profibrotic stimuli (transforming growth factor β) and no effect on the expression of activation markers (α-smooth muscle actin, collagen I and connective tissue growth factor) upon knockout of DPP4 in lung fibroblasts with or without activation with profibrotic stimuli.

Keywords: dipeptidyl peptidase 4; fibroblast; fibrosis; idiopathic pulmonary fibrosis; lung.