Dataset Information

KAI1(CD82) is a key molecule to control angiogenesis and switch angiogenic milieu to quiescent state.

ABSTRACT:

Background

Little is known about endogenous inhibitors of angiogenic growth factors. In this study, we identified a novel endogenous anti-angiogenic factor expressed in pericytes and clarified its underlying mechanism and clinical significance.

Methods

Herein, we found Kai1 knockout mice showed significantly enhanced angiogenesis. Then, we investigated the anti-angiogenic roll of Kai1 in vitro and in vivo.

Results

KAI1 was mainly expressed in pericytes rather than in endothelial cells. It localized at the membrane surface after palmitoylation by zDHHC4 enzyme and induced LIF through the Src/p53 pathway. LIF released from pericytes in turn suppressed angiogenic factors in endothelial cells as well as in pericytes themselves, leading to inhibition of angiogenesis. Interestingly, KAI1 had another mechanism to inhibit angiogenesis: It directly bound to VEGF and PDGF and inhibited activation of their receptors. In the two different in vivo cancer models, KAI1 supplementation significantly inhibited tumor angiogenesis and growth. A peptide derived from the large extracellular loop of KAI1 has been shown to have anti-angiogenic effects to block the progression of breast cancer and retinal neovascularization in vivo.

Conclusions

KAI1 from PC is a novel molecular regulator that counterbalances the effect of angiogenic factors.

SUBMITTER: Lee JW

PROVIDER: S-EPMC8444549 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

KAI1(CD82) is a key molecule to control angiogenesis and switch angiogenic milieu to quiescent state.

Lee Jin-Woo JW Hur Jin J Kwon Yoo-Wook YW Chae Cheong-Whan CW Choi Jae-Il JI Hwang Injoo I Yun Ji-Yeon JY Kang Jin-A JA Choi Young-Eun YE Kim Young Hyun YH Lee Sang Eun SE Lee Cheol C Jo Dong Hyun DH Seok Heeyoung H Cho Byong Seung BS Baek Sung Hee SH Kim Hyo-Soo HS

Journal of hematology & oncology 20210916 1

<h4>Background</h4>Little is known about endogenous inhibitors of angiogenic growth factors. In this study, we identified a novel endogenous anti-angiogenic factor expressed in pericytes and clarified its underlying mechanism and clinical significance.<h4>Methods</h4>Herein, we found Kai1 knockout mice showed significantly enhanced angiogenesis. Then, we investigated the anti-angiogenic roll of Kai1 in vitro and in vivo.<h4>Results</h4>KAI1 was mainly expressed in pericytes rather than in endoth ...[more]

PMID: 34530889

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Project description:BackgroundPeripheral artery disease (PAD), which is caused by atherosclerosis, results in progressive narrowing and occlusion of the peripheral arteries and inhibits blood flow to the lower extremities. Therapeutic angiogenesis is a promising strategy for treating ischemia caused by PAD. Nitric oxide (NO) has been shown to be a key mediator of angiogenesis. It has been demonstrated that β-cyclodextrincan stimulate vessel growth in rabbit corneas. In this study, we assessed the mechanism of action and therapeutic potential of a new angiogenic molecule, (2-hydroxypropyl)-β-cyclodextrin (2HP-β-CD).Methods and results2HP-β-CD significantly increased vascular endothelial growth factor A (VEGF-A) and platelet-derived growth factor BB (PDGF-BB) peptides in human umbilical vein endothelial cells (HUVECs) and also increased basic fibroblast growth factor (bFGF) peptide in human aortic smooth muscle cells (HASMCs). 2HP-β-CD stimulated both proliferation and migration of HUVECs in an endothelial nitric oxide synthase (eNOS)/NO-dependent manner, whereas NO was found to be involved in proliferation, but not migration, of HASMCs. In a unilateral hindlimb ischemia model in mice, 2HP-β-CD injections not only promoted blood flow recovery and increased microvessel densities in ischemic muscle, but also promoted coverage of the vessels with smooth muscle cells, thus stabilizing the vessels. Administration of 2HP-β-CD increased the expression of several angiogenic factors, including VEGF-A, PDGF-BB and transforming growth factor beta-1 (TGF-β1) in ischemic muscle. Injections of 2HP-β-CD also stimulated protein kinase B and extracellular regulated protein kinases (ERK), leading to an increase in phosphorylation of eNOS in ischemic muscle. Treatment with the NOS inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME), showed that stimulation of blood flow induced by 2HP-β-CD was partially dependent on NO.ConclusionsTherapeutic angiogenesis by 2HP-β-CD may be beneficial to patients with PAD.

Dataset Information

KAI1(CD82) is a key molecule to control angiogenesis and switch angiogenic milieu to quiescent state.

Background

Methods

Results

Conclusions

Publications

KAI1(CD82) is a key molecule to control angiogenesis and switch angiogenic milieu to quiescent state.

Similar Datasets

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