Mannose 6-phosphate/insulin-like growth factor 2 receptor in fibrosing phenotypes of diffuse parenchymal lung diseases

Abstract

Background: Mannose 6- phosphate/insulin-like growth factor 2 receptor/CD222 (IGF2R) is largely present intracellularly in the Golgi complex and endosomes, and to a minor extent also on the cell surface. The major functions of IGF2R include regulating the activity of insulin-like growth factor 2 (IGF2) and the transportation of enzymes from the Golgi network to lysosomes. In recent years, a few studies described the role of IGF2R in the process of fibrosis.

Methods: In the study, we analyzed the IGF2R and the enzymes (ADAM17, the enzyme needed for IGF2R shedding from the cell membrane, cathepsins L, S, D the lysosomal enzymes transported by IGF2R intracellularly) in idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis, and sarcoidosis in bronchoalveolar lavage fluid (BALF). The concentration was measured by ELISA and the exosomal or soluble shedding form was proved by Isolation Column based on size exclusion chromatography (iZON qEV) separating molecules and particles by size.

Results: Patients with IPF and HP had significantly higher IGF2R concentrations compared with the control group and sarcoidosis stage I-III. The ADAM17 was increased in the inflammatory type of HP and sarcoidosis stage I-III compared with the fibrosing type of HP and IPF. Cathepsins were increased in IPF and HP compared with sarcoidosis stage I-III. IGF2R was proved to be produced in two forms – exosomal form in IPF and fibrosing type of HP and soluble shedding form in inflammatory HP.

Conclusion: The study proved the exosomal production of IGF2R in IPF and fibrosing phenotype of HP.

VEGA (1/0758/20, 2/0020/17, 2/0152/21)

APVV (16-0452, 20-0513)