Proliferative and Survival Effects of PUMA Promote Angiogenesis

Fan Zhang; Yang Li; Zhongshu Tang; Anil Kumar; Chunsik Lee; Liping Zhang; Chaoyong Zhu; Anne Klotzsche-von Ameln; Bin Wang; Zhiqin Gao; Shizhuang Zhang; Harald F. Langer; Xu Hou; Lasse Jensen; Wenxin Ma; Wai Wong; Triantafyllos Chavakis; Yizhi Liu; Yihai Cao; Xuri Li

doi:10.1016/j.celrep.2012.09.023

Cell Reports (Nov 2012)

Proliferative and Survival Effects of PUMA Promote Angiogenesis

Fan Zhang,
Yang Li,
Zhongshu Tang,
Anil Kumar,
Chunsik Lee,
Liping Zhang,
Chaoyong Zhu,
Anne Klotzsche-von Ameln,
Bin Wang,
Zhiqin Gao,
Shizhuang Zhang,
Harald F. Langer,
Xu Hou,
Lasse Jensen,
Wenxin Ma,
Wai Wong,
Triantafyllos Chavakis,
Yizhi Liu,
Yihai Cao,
Xuri Li

Affiliations

Fan Zhang: National Eye Institute, National Institutes of Health, Rockville, MD 20852, USA
Yang Li: National Eye Institute, National Institutes of Health, Rockville, MD 20852, USA
Zhongshu Tang: National Eye Institute, National Institutes of Health, Rockville, MD 20852, USA
Anil Kumar: National Eye Institute, National Institutes of Health, Rockville, MD 20852, USA
Chunsik Lee: National Eye Institute, National Institutes of Health, Rockville, MD 20852, USA
Liping Zhang: National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892, USA
Chaoyong Zhu: School of Public Health, NanTong University, 9 Seyuan Road, Nantong 226019, P.R. China
Anne Klotzsche-von Ameln: Division of Vascular Inflammation, Diabetes and Kidney, Department of Medicine, and Institute of Physiology, University Dresden, Dresden 0351 463-0, Germany
Bin Wang: Medical Imaging Institute, Shandong Province Characteristical Key Subject, Medical Imaging and Nuclear Medicine, Binzhou Medical University, Yantai, 264003 P.R. China
Zhiqin Gao: Department of Cell Biology, Weifang Medical University, Weifang, 261053, P.R. China
Shizhuang Zhang: Department of Radiology, Medical Imaging Centre of the Affiliated Hospital, Weifang Medical University, Weifang, 261053, P.R. China
Harald F. Langer: Department of Cardiovascular Medicine, University of Tübingen, Tübingen 72074, Germany
Xu Hou: Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi`an, Shaanxi 710032, China
Lasse Jensen: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden
Wenxin Ma: National Eye Institute, National Institutes of Health, Rockville, MD 20852, USA
Wai Wong: National Eye Institute, National Institutes of Health, Rockville, MD 20852, USA
Triantafyllos Chavakis: Division of Vascular Inflammation, Diabetes and Kidney, Department of Medicine, and Institute of Physiology, University Dresden, Dresden 0351 463-0, Germany
Yizhi Liu: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, P.R. China
Yihai Cao: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden
Xuri Li: National Eye Institute, National Institutes of Health, Rockville, MD 20852, USA

DOI: https://doi.org/10.1016/j.celrep.2012.09.023
Journal volume & issue: Vol. 2, no. 5
pp. 1272 – 1285

Abstract

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The p53 upregulated modulator of apoptosis (PUMA) is known as an essential apoptosis inducer. Here, we report the seemingly paradoxical finding that PUMA is a proangiogenic factor critically required for the proliferation and survival of vascular and microglia cells. Strikingly, Puma deficiency by genetic deletion or small hairpin RNA knockdown inhibited developmental and pathological angiogenesis and reduced microglia numbers in vivo, whereas Puma gene delivery increased angiogenesis and cell survival. Mechanistically, we revealed that PUMA plays a critical role in regulating autophagy by modulating Erk activation and intracellular calcium level. Our findings revealed an unexpected function of PUMA in promoting angiogenesis and warrant more careful investigations into the therapeutic potential of PUMA in treating cancer and degenerative diseases.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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