Reduction of renal interstitial fibrosis by targeting Tie2 in vascular endothelial cells.

Abstract

BACKGROUND:

Tie2, a functional angiopoietin receptor, is expressed in vascular endothelial cells and plays an important role in angiogenesis and vascular stability. This study aimed to evaluate the effects of an agonistic Tie2 signal on renal interstitial fibrosis (RIF) and elucidate the underlying mechanisms.

METHODS:

We established an in vivo mouse model of folic acid-induced nephropathy (FAN) and an in vitro model of lipopolysaccharide-stimulated endothelial cell injury, then an agonistic Tie2 monoclonal antibody (Tie2 mAb) was used to intervent these processes. The degree of tubulointerstitial lesions and related molecular mechanisms were determined by histological assessment, immunohistochemistry, western blotting, and qPCR.

RESULTS:

Tie2 mAb attenuated RIF and reduced the level of fibroblast-specific protein 1 (FSP1). Further, it suppressed vascular cell adhesion molecule-1 (VCAM-1) and increased CD31 density in FAN. In the in vitro model, Tie2 mAb was found to decrease the expression of VCAM-1, Bax, and α-smooth muscle actin (α-SMA).

CONCLUSIONS:

The present findings indicate that the agonistic Tie2 mAb exerted vascular protective effects and ameliorated RIF via inhibition of vascular inflammation, apoptosis, and fibrosis. Therefore, Tie2 may be a potential target for the treatment of this disease.

IMPACT:

This is the first report to confirm that an agonistic Tie2 monoclonal antibody can reduce renal interstitial fibrosis in folic acid-induced nephropathy in mice. This mechanism possibly involves vascular protective effects brought about by inhibition of vascular inflammation, apoptosis and fibrosis. Our data show that Tie2 signal may be a novel, endothelium-specific target for the treatment of tubulointerstitial fibrosis.

• Authors: Lu Jiang, Xiaohan Hu, Yajun Feng, Zhen Wang, Hanyun Tang, Qiang Lin, Yunyan Shen, Yun Zhu, Qinying Xu, Xiaozhong Li
• Journal: Pediatric research (Pediatr Res) Vol. 95 Issue 4 Pg. 959-965 (Mar 2024) ISSN: 1530-0447 [Electronic] United States
• PMID: 38012310 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s).

Chemical References

• Receptor, TIE-2
• Vascular Cell Adhesion Molecule-1
• Antibodies, Monoclonal
• Folic Acid
• Angiopoietin-1
• Angiopoietin-2

Topics

• Mice
• Animals
• Endothelial Cells (metabolism)
• Receptor, TIE-2 (metabolism)
• Vascular Cell Adhesion Molecule-1
• Fibrosis
• Antibodies, Monoclonal (pharmacology)
• Kidney Diseases (chemically induced)
• Folic Acid
• Inflammation
• Angiopoietin-1
• Angiopoietin-2