NDST1-dependent heparan sulfate regulates BMP signaling and internalization in lung development

doi:10.1242/jcs.034736

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 新药研究国家重点实验室

	NDST1-dependent heparan sulfate regulates BMP signaling and internalization in lung development
	Hu, Zhonghua 2; Wang, Chaochen 2; Xiao, Ying 3; Sheng, Nengyin 1; Chen, Yibin 2; Xu, Ye 2; Zhang, Liang 2; Mo, Wei 2; Jing, Naihe 1; Hu, Gengxi 2
刊名	JOURNAL OF CELL SCIENCE
	2009-04-15
卷号	122 期号:8 页码:1145-1154
关键词	NDST1 BMP signaling Lung development
ISSN号	0021-9533
DOI	10.1242/jcs.034736
文献子类	Article
英文摘要	Heparan sulfate proteoglycans (HSPGs) are required for various signaling pathways, one of which is the bone morphogenetic protein (BMP) signaling pathway. N-deacetylase/N-sulfotransferase-1 (NDST1) participates in synthesizing heparan sulfate (HS) chains of HSPGs, and is involved in bone and lung development. Here, we report that in spite of the redundant expression of Ndst2, Ndst3 and Ndst4 genes, Ndst1(-/-) mice display defective differentiation of lung cells and increased cell proliferation. Loss of Ndst1 in the lung enhances downstream BMP signaling in vivo. Noggin, which is an antagonist of BMP, can rescue the Ndst1(-/-) lung morphogenetic defects in explant cultures. Further studies in vitro indicated that loss of Ndst1 significantly impairs BMP internalization by decreasing BMP binding to endogenous HS. Exogenous heparin can rescue both the BMP signaling and BMP internalization abnormalities in Ndst1(-/-) lung. Thus, we propose that HS regulates BMP signaling by controlling the balance between BMP binding to HS, and that BMP receptors and NDST1-dependent modification are essential for this process. The results suggest that NDST1-dependent HS is essential for proper functioning of BMP in embryonic lung development.
资助项目	Minster for Science and Technology[G1998051007] ; Chinese High-Tech RD Program[(863)-2001AA231011] ; Chinese High-Tech RD Program[0022Z2002]
WOS关键词	N-DEACETYLASE/N-SULFOTRANSFERASE ; MOUSE EMBRYONIC LUNG ; BONE MORPHOGENETIC PROTEIN-4 ; BRANCHING-MORPHOGENESIS ; MOLECULAR-CLONING ; SPEMANN ORGANIZER ; GENE-EXPRESSION ; LACRIMAL-GLAND ; MAST-CELLS ; PROTEOGLYCANS
WOS研究方向	Cell Biology
语种	英语
出版者	COMPANY BIOLOGISTS LTD
WOS记录号	WOS:000264777700011
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279264]
专题	新药研究国家重点实验室中科院受体结构与功能重点实验室
通讯作者	Hu, Gengxi
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Key Lab Stem Cell Biol,Lab Mol Cell Biol, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Mol Biol, Shanghai 200031, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China;
推荐引用方式 GB/T 7714	Hu, Zhonghua,Wang, Chaochen,Xiao, Ying,et al. NDST1-dependent heparan sulfate regulates BMP signaling and internalization in lung development[J]. JOURNAL OF CELL SCIENCE,2009,122(8):1145-1154.
APA	Hu, Zhonghua.,Wang, Chaochen.,Xiao, Ying.,Sheng, Nengyin.,Chen, Yibin.,...&Hu, Gengxi.(2009).NDST1-dependent heparan sulfate regulates BMP signaling and internalization in lung development.JOURNAL OF CELL SCIENCE,122(8),1145-1154.
MLA	Hu, Zhonghua,et al."NDST1-dependent heparan sulfate regulates BMP signaling and internalization in lung development".JOURNAL OF CELL SCIENCE 122.8(2009):1145-1154.