| A fetal wound healing program after intrauterine bile duct injury may contribute to biliary atresia | |
de Jong, Iris EM1,2; Hunt, Mallory L3; Chen, Dongning2,4,5; Du Y(杜宇)2,6,7 ; Llewellyn, Jessica2; Gupta, Kapish2; Li, David2; Erxleben, Dorothea8; Rivas, Felipe8; Hall, Adam R8,9; Furth, Emma E10; Naji, Ali11; Liu, Chengyang11; Dhand, Abhishek1,4; Burdick, Jason A12; Davey, Marcus G13; Flake, Alan W13; Porte, Robert J1; Russo, Pierre A14; Gaynor, J William3; Wells, Rebecca G2,4,5,10,15
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| Corresponding Author | Wells, Rebecca G.([email protected]) |
| Source Publication | JOURNAL OF HEPATOLOGY
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| 2023-12-01 | |
| Volume | 79Issue:6Pages:13 |
| ISSN | 0168-8278 |
| Abstract | 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/). |
| Keyword | biliary atresia hyaluronic acid peribiliary glands cholangiocyte cholangiopathy |
| DOI | 10.1016/j.jhep.2023.08.010 |
| Indexed By | SCI |
| Language | 英语 |
| WOS ID | WOS:001128644200001 |
| WOS Keyword | HYALURONIC-ACID ; COLLAGEN DEPOSITION ; EXPRESSION ; STEROIDS ; SYSTEM |
| WOS Research Area | Gastroenterology & Hepatology |
| WOS Subject | Gastroenterology & Hepatology |
| Funding Project | NIH[R01DK119290] ; NIH[R01GM134226] ; NIH[P41EB020594] ; Fred and Suzanne Biesecker Foundation ; Fulbright Foundation ; International Liver Transplantation Society |
| Funding Organization | NIH ; Fred and Suzanne Biesecker Foundation ; Fulbright Foundation ; International Liver Transplantation Society |
| Classification | 一类 |
| Ranking | 3+ |
| Contributor | Wells, Rebecca G. |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://dspace.imech.ac.cn/handle/311007/93783 |
| Collection | 微重力重点实验室 |
| Affiliation | 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 |
| Recommended Citation 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.Rp_Au:Wells, Rebecca G. |
| 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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| Jp2023Fa170.pdf（6669KB） | 期刊论文 | 出版稿 | 开放获取 | CC BY-NC-SA | View Download | |
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