A fetal wound healing program after intrauterine bile duct injury may contribute to biliary atresia
文献类型：期刊论文
| Author | de Jong, Iris E. M.14,15; Hunt, Mallory L.13; Chen, Dongning11,12,14; Du, Yu9,10,14 ; Llewellyn, Jessica14; Gupta, Kapish14; Li, David14; Erxleben, Dorothea8; Rivas, Felipe8; Hall, Adam R.7,8
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| Source | JOURNAL OF HEPATOLOGY
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| Issued Date | 2023-12-01 |
| Volume | 79Issue:6Pages:13 |
| Keyword | biliary atresia hyaluronic acid peribiliary glands cholangiocyte cholangiopathy |
| ISSN | 0168-8278 |
| DOI | 10.1016/j.jhep.2023.08.010 |
| Corresponding Author | Wells, Rebecca G.(rgwells@pennmedicine.upenn.edu) |
| English 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/). |
| WOS Keyword | HYALURONIC-ACID ; COLLAGEN DEPOSITION ; EXPRESSION ; STEROIDS ; SYSTEM |
| Funding Project | NIH[R01DK119290] ; NIH[R01GM134226] ; NIH[P41EB020594] ; Fred and Suzanne Biesecker Foundation ; Fulbright Foundation ; International Liver Transplantation Society |
| WOS Research Area | Gastroenterology & Hepatology |
| Language | 英语 |
| WOS ID | WOS:001128644200001 |
| Funding Organization | NIH ; Fred and Suzanne Biesecker Foundation ; Fulbright Foundation ; International Liver Transplantation Society |
| 源URL | [http://dspace.imech.ac.cn/handle/311007/93782]  |
| Collection | 力学研究所_国家微重力实验室 |
| Corresponding Author | Wells, Rebecca G. |
| Affiliation | 1.Univ Penn, Perelman Sch Med, Dept Med, Div Gastroenterol & Hepatol, Philadelphia, PA 19104 USA 2.Childrens Hosp Philadelphia, Dept Pathol, Lab Med, Philadelphia, PA USA 3.Childrens Hosp Philadelphia, Ctr Fetal Res, Dept Surg, Philadelphia, PA USA 4.Univ Colorado, Dept Chem & Biol Engn, Boulder, CO USA 5.Univ Penn, Perelman Sch Med, Dept Surg, Philadelphia, PA USA 6.Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA 7.Wake Forest Sch Med, Comprehens Canc Ctr, Winston Salem, NC USA 8.Virginia Tech Wake Forest Univ, Wake Forest Sch Med, Sch Biomed Engn & Sci, Winston Salem, NC USA 9.Chinese Acad Sci, Inst Mech, Beijing Key Lab Engn Construct & Mechanobiol, Beijing, Peoples R China 10.Chinese Acad Sci, Ctr Biomech & Bioengn, Key Lab Micrograv, Natl Micrograv Lab, Beijing, Peoples R China |
| Recommended Citation GB/T 7714 | de Jong, Iris E. M.,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 E. M..,Hunt, Mallory L..,Chen, Dongning.,Du, Yu.,Llewellyn, Jessica.,...&杜宇.(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 E. M.,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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