The synthetic toxin biliatresone causes biliary atresia in mice

Yang, Yifan; Wang, Junfeng; Zhan, Yong; Chen, Gong; Shen, Zhen; Zheng, Shan; Dong, Rui

doi:10.1038/s41374-020-0467-7

Cited by 25 publications

(39 citation statements)

References 32 publications

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“… Biliatresone treatment of Balb/c mouse pups (0-3 days) Neonatal mice injected with biliatresone developed biliary obstruction and dysplasia or absence of extrahepatic bile ducts Yang et al., (2020). REF 38 Morpholino-gene knockdown or CRISPR/Cas9 genome editing Knockdown or knockout of BA candidate genes resulted in biliary developmental defects in zebrafish larvae Cui et al., (2013). REF 6 Tang et al., (2016).…”

Section: Technology Platforms Underpinning Biliary Atresia Researchmentioning

confidence: 99%

Biliary Atresia – emerging diagnostic and therapy opportunities

et al. 2021

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Section: Technology Platforms Underpinning Biliary Atresia Researchmentioning

confidence: 99%

Biliary Atresia – emerging diagnostic and therapy opportunities

et al. 2021

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“…The isoflavonoid biliatresone has been shown to selectively destruct the extrahepatic cholangiocytes in zebrafish (47). Biliatresone also mimicked BA in mice and was studied in cell cultures (48)(49)(50). These studies also investigated the mechanism of action by which the toxin could accomplish toxicity to the cholangiocytes.…”

Section: Etiology Of Biliary Atresiamentioning

confidence: 99%

“…Microtubules are essential for lumen formation and polarity of epithelial cells and disruption of the tubules results in increased epithelial permeability and reduced cell-to-cell contact (49). RNA sequencing revealed downregulation of cell adhesion related genes (48). Therefore, Yang et al speculate that a yet unidentified toxin may cause BA in humans by depletion of GSH (48).…”

Section: Etiology Of Biliary Atresiamentioning

confidence: 99%

“…RNA sequencing revealed downregulation of cell adhesion related genes (48). Therefore, Yang et al speculate that a yet unidentified toxin may cause BA in humans by depletion of GSH (48).…”

Section: Etiology Of Biliary Atresiamentioning

confidence: 99%

“…Lertudomphonwanit et al found that MMP-7 was released by cholangiocytes in response to injury, although it was found in an experimental model of BA in mice (125). Interestingly, using RNA sequencing techniques, it was found that there was upregulation of the MMP-7 gene in liver samples of mice with BA induced by biliatresone (48).…”

Section: Matrix Metalloproteinase-7 (Mmp-7)mentioning

confidence: 99%

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Current Concepts of Biliary Atresia and Matrix Metalloproteinase-7: A Review of Literature

et al. 2020

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Biliary atresia (BA) is a rare cholangiopathy of infancy in which the bile ducts obliterate, leading to profound cholestasis and liver fibrosis. BA is hypothesized to be caused by a viral insult that leads to over-activation of the immune system. Patients with BA are surgically treated with a Kasai portoenterostomy (KPE), which aims to restore bile flow from the liver to the intestines. After KPE, progressive liver fibrosis is often observed in BA patients, even despite surgical success and clearance of their jaundice. The innate immune response is involved during the initial damage to the cholangiocytes and further differentiation of the adaptive immune response into a T-helper 1 cell (Th1) response. Multiple studies have shown that there is continuing elevation of involved cytokines that can lead to the progressive liver fibrosis. However, the mechanism by which the progressive injury occurs is not fully elucidated. Recently, matrix metalloproteinase-7 (MMP-7) has been investigated to be used as a biomarker to diagnose BA. MMPs are involved in extracellular matrix (ECM) turnover, but also have non-ECM related functions. The role of MMP-7 and other MMPs in liver fibrosis is just starting to be elucidated. Multiple studies have shown that serum MMP-7 measurements are able to accurately diagnose BA in a cohort of cholestatic patients while hepatic MMP-7 expression correlated with BA-related liver fibrosis. While the mechanism by which MMP-7 can be involved in the pathophysiology of BA is unclear, MMP-7 has been investigated in other fibrotic pathologies such as renal and idiopathic pulmonary fibrosis. MMP-7 is involved in Wnt/β-catenin signaling, reducing cell-to-cell contact by shedding of E-cadherin, amplifying inflammation and fibrosis via osteopontin (OPN) and TNF-α while it also appears to play a role in induction of angiogenesis This review aims to describe the current understandings of the pathophysiology of BA. Subsequently, we describe how MMP-7 is involved in other pathologies, such as renal and pulmonary fibrosis. Then, we propose how MMP-7 can potentially be involved in BA. By doing this, we aim to describe the putative role of MMP-7 as a prognostic biomarker in BA and to provide possible new therapeutic and research targets that can be investigated in the future.

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A novel model of injured liver ductal organoids to investigate cholangiocyte apoptosis with relevance to biliary atresia

Chusilp

Lee

et al. 2020

Pediatr Surg Int

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The synthetic toxin biliatresone causes biliary atresia in mice

Cited by 25 publications

References 32 publications

Biliary Atresia – emerging diagnostic and therapy opportunities

Biliary Atresia – emerging diagnostic and therapy opportunities

Current Concepts of Biliary Atresia and Matrix Metalloproteinase-7: A Review of Literature

A novel model of injured liver ductal organoids to investigate cholangiocyte apoptosis with relevance to biliary atresia

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