A fetal wound healing program after intrauterine bile duct injury may contribute to biliary atresia

doi:10.1016/j.jhep.2023.08.010

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	A fetal wound healing program after intrauterine bile duct injury may contribute to biliary atresia
	de Jong, Iris EM 1,2; Hunt, Mallory L 3; Chen, Dongning 2,4,5; Du Y(杜宇)2,6,7 ; Llewellyn, Jessica 2; Gupta, Kapish 2; Li, David 2; Erxleben, Dorothea 8; Rivas, Felipe 8; Hall, Adam R 8,9; Furth, Emma E 10; Naji, Ali 11; Liu, Chengyang 11; Dhand, Abhishek 1,4; Burdick, Jason A 12; Davey, Marcus G 13; Flake, Alan W 13; Porte, Robert J 1; Russo, Pierre A 14; Gaynor, J William 3; Wells, Rebecca G 2,4,5,10,15
通讯作者	Wells, Rebecca G.(rgwells@pennmedicine.upenn.edu)
发表期刊	JOURNAL OF HEPATOLOGY
	2023-12-01
卷号	79 期号:6 页码:13
ISSN	0168-8278
摘要	Background & Aims: Biliary atresia (BA) is an obstructive cholangiopathy that initially affects the extrahepatic bile ducts (EHBDs) of neonates. The etiology is uncertain, but evidence points to a prenatal cause. Fetal tissues have increased levels of hyaluronic acid (HA), which plays an integral role in fetal wound healing. The objective of this study was to determine whether a program of fetal wound healing is part of the response to fetal EHBD injury.Methods: Mouse, rat, sheep, and human EHBD samples were studied at different developmental time points. Models included a fetal sheep model of prenatal hypoxia, human BA EHBD remnants and liver samples taken at the time of the Kasai procedure, EHBDs isolated from neonatal rats and mice, and spheroids and other models generated from primary neonatal mouse cholangiocytes. Results: A wide layer of high molecular weight HA encircling the lumen was characteristic of the normal perinatal but not adult EHBD. This layer, which was surrounded by collagen, expanded in injured ducts in parallel with extensive peribiliary gland hyperplasia, increased mucus production and elevated serum bilirubin levels. BA EHBD remnants similarly showed increased HA centered around ductular structures compared with age-appropriate controls. High molecular weight HA typical of the fetal/ neonatal ducts caused increased cholangiocyte spheroid growth, whereas low molecular weight HA induced abnormal epithelial morphology; low molecular weight HA caused matrix swelling in a bile duct-on-a-chip device. Conclusion: The fetal/neonatal EHBD, including in human EHBD remnants from Kasai surgeries, demonstrated an injury response with prolonged high levels of HA typical of fetal wound healing. The expanded peri-luminal HA layer may swell and lead to elevated bilirubin levels and obstruction of the EHBD.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
关键词	biliary atresia hyaluronic acid peribiliary glands cholangiocyte cholangiopathy
DOI	10.1016/j.jhep.2023.08.010
收录类别	SCI
语种	英语
WOS记录号	WOS:001128644200001
关键词[WOS]	HYALURONIC-ACID ; COLLAGEN DEPOSITION ; EXPRESSION ; STEROIDS ; SYSTEM
WOS研究方向	Gastroenterology & Hepatology
WOS类目	Gastroenterology & Hepatology
资助项目	NIH[R01DK119290] ; NIH[R01GM134226] ; NIH[P41EB020594] ; Fred and Suzanne Biesecker Foundation ; Fulbright Foundation ; International Liver Transplantation Society
项目资助者	NIH ; Fred and Suzanne Biesecker Foundation ; Fulbright Foundation ; International Liver Transplantation Society
论文分区	一类
力学所作者排名	3+
RpAuthor	Wells, Rebecca G.
引用统计	被引频次：1[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://dspace.imech.ac.cn/handle/311007/93783
专题	微重力重点实验室
作者单位	1.Univ Groningen, Univ Med Ctr Groningen, Dept Surg, Sect Hepatobiliary Surg & Liver Transplantat, Groningen, Netherlands; 2.Univ Penn, Dept Med, Philadelphia, PA USA; 3.Childrens Hosp Philadelphia, Div Cardiothorac Surg, Philadelphia, PA USA; 4.Univ Penn, Dept Bioengn, Philadelphia, PA USA; 5.Univ Penn, Ctr Engn Mechanobiol, Philadelphia, PA USA; 6.Chinese Acad Sci, Ctr Biomech & Bioengn, Key Lab Micrograv, Natl Micrograv Lab, Beijing, Peoples R China; 7.Chinese Acad Sci, Inst Mech, Beijing Key Lab Engn Construct & Mechanobiol, Beijing, Peoples R China; 8.Virginia Tech Wake Forest Univ, Wake Forest Sch Med, Sch Biomed Engn & Sci, Winston Salem, NC USA; 9.Wake Forest Sch Med, Comprehens Canc Ctr, Winston Salem, NC USA; 10.Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA; 11.Univ Penn, Perelman Sch Med, Dept Surg, Philadelphia, PA USA; 12.Univ Colorado, Dept Chem & Biol Engn, Boulder, CO USA; 13.Childrens Hosp Philadelphia, Ctr Fetal Res, Dept Surg, Philadelphia, PA USA; 14.Childrens Hosp Philadelphia, Dept Pathol, Lab Med, Philadelphia, PA USA; 15.Univ Penn, Perelman Sch Med, Dept Med, Div Gastroenterol & Hepatol, Philadelphia, PA 19104 USA
推荐引用方式 GB/T 7714	de Jong, Iris EM,Hunt, Mallory L,Chen, Dongning,et al. A fetal wound healing program after intrauterine bile duct injury may contribute to biliary atresia[J]. JOURNAL OF HEPATOLOGY,2023,79,6,:13.
APA	de Jong, Iris EM.,Hunt, Mallory L.,Chen, Dongning.,杜宇.,Llewellyn, Jessica.,...&Wells, Rebecca G.(2023).A fetal wound healing program after intrauterine bile duct injury may contribute to biliary atresia.JOURNAL OF HEPATOLOGY,79(6),13.
MLA	de Jong, Iris EM,et al."A fetal wound healing program after intrauterine bile duct injury may contribute to biliary atresia".JOURNAL OF HEPATOLOGY 79.6(2023):13.

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