Inhibition of LPA-LPAR1 and VEGF-VEGFR2 Signaling in IPF Treatment

Drug Des Devel Ther. 2023 Sep 2:17:2679-2690. doi: 10.2147/DDDT.S415453. eCollection 2023.

Abstract

Due to the complex mechanism and limited treatments available for pulmonary fibrosis, the development of targeted drugs or inhibitors based on their molecular mechanisms remains an important strategy for prevention and treatment. In this paper, the downstream signaling pathways mediated by VEGFR and LPAR1 in pulmonary cells and the role of these pathways in pulmonary fibrosis, as well as the current status of drug research on the targets of LPAR1 and VEGFR2, are described. The mechanism by which these two pathways regulate vascular leakage and collagen deposition leading to the development of pulmonary fibrosis are analyzed, and the mutual promotion of the two pathways is discussed. Here we propose the development of drugs that simultaneously target LPAR1 and VEGFR2, and discuss the important considerations in targeting and safety.

Keywords: LPAR1; VEGFR2; idiopathic pulmonary fibrosis.

Publication types

  • Review

MeSH terms

  • Drug Delivery Systems
  • Humans
  • Pulmonary Fibrosis*
  • Receptors, Lysophosphatidic Acid
  • Vascular Endothelial Growth Factor A

Substances

  • Vascular Endothelial Growth Factor A
  • LPAR1 protein, human
  • Receptors, Lysophosphatidic Acid

Grants and funding

This work was supported by grants from National Nature Foundation (82160846), provincial Natural Science Foundation (20JR10RA321), Gansu Provincial Higher Education Innovation Fund Project (2021A-085).