Abstract 12131: LMO2 Regulates Endothelial Proliferation, Angiogenesis and Tissue Regeneration
Introduction: LIM domain only 2 (LMO2) is a key transcription factor of embryonic angiogenesis. However, its role in adult endothelial function and tissue regeneration is unclear.
Methods: In vitro loss- and gain-of-function studies on LMO2 were performed in human umbilical vein endothelial cells (HUVEC) with lentiviral overexpression (OE) or shRNA knock down (KD) of LMO2 respectively. LMO2 gene expression and protein level was examined by RT-PCR and western blot respectively. Cell cycle was examined by PI staining and FACS analysis. Angiogenesis was examined by network formation assay on matrigel. ChIP-PCR was used to examine the LMO2 complex binding to chromatin. Vascular and tissue regeneration was examined by caudal fin regeneration in zebrafish model.
Results: LMO2 KD impaired endothelial proliferation and angiogenesis. LMO2 controls the G1/S transition in endothelial cells through transcriptional regulation of CDK2 and CDK4 examined by RT, western blot and ChIP, and also influences the expression of CyclinD1 and Cyclin A1. LMO2 KD downregulated a network of angiogenic genes. Among them, LMO2 regulated TGFβ through binding to the proximal promoter of TGFB1. In a zebrafish model of caudal fin regeneration, lmo2 gene was upregulated at day 5 post resection. In this model, lmo2 KD by vivo-morpholino injection reduced BrdU incorporation in endothelial cells, impaired neoangiogenesis, and substantially delayed caudal fin regeneration.
Conclusions: LMO2 is a critical transcription factor regulating adult endothelial proliferation and angiogenesis, and in adult animals regulates vascular and tissue regeneration.
Author Disclosures: S. Meng: None. G. Matrone: None. W. Wong: None. J. Cooke: None.
- © 2016 by American Heart Association, Inc.