Endoglin is a conserved regulator of vasculogenesis in zebrafish – implications for hereditary haemorrhagic telangiectasia
Authors: Bao Liu
Fang Zhou
Jingyu Chen
Jun Yang
Xiuli Zhao
Ding Zhang
Journal: Bioscience reports (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: endoglin; endothelial cells; vasculogenesis; zebrafish.
Affiliations: Department of Cell Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China., Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing 100005, China., Department of Vascular Surgery, Peking Union College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100005, China., Wuxi Lung Transplant Center, Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi 214023, China., Department of Cell Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China .

Abstract:  Hereditary haemorrhagic telangiectasia (HHT) is a progressive vascular disease with high mortality and prevalence. There is no effective treatment of HHT due to the lack of comprehensive knowledge of its underlying pathological mechanisms. The majority of HHT1 patients carry endoglin (ENG) mutations. Here, we used Danio rerio (zebrafish) as an in vivo model to investigate the effects of endoglin knockdown on vascular development. According to phylogenetic analyses and amino acid sequence similarity analyses, we confirmed that endoglin is conserved in vertebrates and descended from a single common ancestor. Endoglin is highly expressed in the vasculature beginning at the segmentation period in zebrafish. Upon endoglin knockdown by morpholinos, we observed disruption in the intersegmental vessels (ISVs) and decreased expression of several vascular markers. RNA sequencing (RNA-Seq) results implied that the BMP-binding endothelial regulator (bmper) is a gene affected by endoglin knockdown. Rescue experiments demonstrated that overexpression of bmper significantly increased the number of endothelial cells (ECs) and reduced the defects at ISVs in zebrafish. Moreover, there was enhanced tube formation in ENG mutant ECs derived from a HHT patient after human recombinant BMPER (hrBMPER) stimulation. Taken together, our results suggest that bmper, a potential downstream gene of ENG, could be targeted to improve vascular integrity in HHT. 

Retracted: No

PubPeer comments:
 Figure 4C appears to include a repeated image, although annotated differently and with different horizontal dimensions. The authors please explain what happened? Arrows in original. *** ![file] *** Closeup ![file] *** Inverse image ![file] , 
 Hello, I m the first author of the article. My name is Ding Zhang. Thanks for the careful read and concerns. We are so sorry to make the mistake in article. After we carefully checked the orginal data and found the mistake came from the typeset in PPT. The original version covered the updated figure when we aligned different group in PPT. Moreover, we may ignore the error in the revised manuscript since the expression of Imo2 and hey2 is so low in knockdown group. Here, we provided the corrected version and would contact with the press to update the error as soon as possible. , 
 ![file] ,