南方科技大学知识苑(SUSTech KC): Defective CFTR promotes intestinal proliferation via inhibition of the hedgehog pathway during cystic fibrosis

题名	Defective CFTR promotes intestinal proliferation via inhibition of the hedgehog pathway during cystic fibrosis
作者	Liu, Kaisheng 1,2; Wang, Xiao 1; Zou, Chang 1; Zhang, Jieting 2; Chen, Hao 2,3; Tsang, Lailing 2; Yu, Mei Kuen 2; Chung, Yiu Wa 2; Wang, Jianhong 1; Dai, Yong 1; Liu, Yang 2,4,6; Zhang, Xiaohu 2,5,6
通讯作者	Zou, Chang; Dai, Yong; Liu, Yang; Zhang, Xiaohu
发表日期	2019
DOI	10.1016/j.canlet.2018.12.018
发表期刊	CANCER LETTERS 影响因子和分区
ISSN	0304-3835
EISSN	1872-7980
卷号	446页码:15-24
摘要	Hyperproliferation occurs in a variety of tissues and organs during cystic fibrosis (CF). However, the associated molecular mechanisms remain elusive. We investigated the molecular link between cystic fibrosis transmembrane conductance regulator (CFTR) defects and hyperproliferation, and showed that the length of the entire gastrointestinal tract was longer and the intestinal crypts were deeper in CF mice compared to those in wild-type animals. PCNA expression increased in CF mouse intestines and CFTR-knockdown cells. Villinl, an intestinal differentiation marker, was downregulated in CF mice. Ihh and Glil were significantly downregulated, whereas TCF4 was activated in CF mouse intestines and CFTR-knockdown Caco2 cells. Importantly, beta-catenin activators rescued Gli1 suppression, suggesting that hedgehog signaling might be mediated by the Wnt/beta-catenin pathway in the absence of functional CFTR. Moreover, PCNA positivity in the crypts of CF mice was alleviated by LiCl, which activates Wnt/beta-catenin signaling. Further, a strong positive correlation was observed between the expression of CITH and Ihh in intestines. Our study revealed a previously unidentified role of CFTR in regulating hedgehog signaling through beta-catenin, providing novel insights into the physiological function of CFTR and CF-related diseases.
关键词	CFTR beta-catenin Hedgehog Small intestine Proliferation
相关链接	[来源记录]
收录类别	SCI
语种	英语
学校署名	第一 ; 通讯
资助项目	National Key Research and Development Program of China[2018YFC1002801]
WOS研究方向	Oncology
WOS类目	Oncology
WOS记录号	WOS:000458940700002
出版者	ELSEVIER IRELAND LTD
ESI学科分类	CLINICAL MEDICINE
来源库	Web of Science
引用统计	被引频次[WOS]：9
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/26708
专题	南方科技大学第一附属医院
作者单位	1.Southern Univ Sci & Technol, Affiliated Hosp 1, Jinan Univ, Clin Med Coll 2,Shenzhen Peoples Hosp, Shenzhen 518020, Guangdong, Peoples R China 2.Chinese Univ Hong Kong, Sch Biomed Sci, Epithelial Cell Biol Res Ctr, Key Lab Regenerat Med,Minist Educ China,Fac Med, Hong Kong, Peoples R China 3.Guangdong Univ Technol, Sch Biomed & Pharmaceut Sci, Guangzhou 510000, Guangdong, Peoples R China 4.Sichuan Univ, West China Univ Hosp 2, Dept Pediat, Chengdu 610041, Sichuan, Peoples R China 5.Sichuan Univ, West China Univ Hosp 2, Sichuan Univ Chinese Univ Hong Kong Joint Lab Rep, Chengdu 610041, Sichuan, Peoples R China 6.Sichuan Univ, West China Univ Hosp 2, Minist Educ, Key Lab Birth Defects & Related Dis Women & Child, Chengdu 610041, Sichuan, Peoples R China
第一作者单位	南方科技大学第一附属医院
通讯作者单位	南方科技大学第一附属医院
第一作者的第一单位	南方科技大学第一附属医院
推荐引用方式 GB/T 7714	Liu, Kaisheng,Wang, Xiao,Zou, Chang,et al. Defective CFTR promotes intestinal proliferation via inhibition of the hedgehog pathway during cystic fibrosis[J]. CANCER LETTERS,2019,446:15-24.
APA	Liu, Kaisheng.,Wang, Xiao.,Zou, Chang.,Zhang, Jieting.,Chen, Hao.,...&Zhang, Xiaohu.(2019).Defective CFTR promotes intestinal proliferation via inhibition of the hedgehog pathway during cystic fibrosis.CANCER LETTERS,446,15-24.
MLA	Liu, Kaisheng,et al."Defective CFTR promotes intestinal proliferation via inhibition of the hedgehog pathway during cystic fibrosis".CANCER LETTERS 446(2019):15-24.