Actomyosin Contractility Drives Bile Regurgitation as an Early Homeostatic Response to Increased Biliary Pressure in Obstructive Cholestasis

Gupta, Kapish; Li, Qiushi; Fan, Jun; Fong, Eliza Li Shan; Song, Ziwei; Mo, Shupei; Tang, Haoyu; Ng, Inn Chuan; Ng, Chan Way; Pawijit, Pornteera; Zhuo, Shuangmu; Dong, Chongying; Low, Boon Chuan; Wee, Aileen; Dan, Yock Young; Kanchanawong, Pakorn; So, Peter T. C.; Viasnoff, Virgile; Yu, Hanry

doi:10.1101/077792

Cited by 3 publications

(3 citation statements)

References 45 publications

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“…Canaliculi are known to contract autonomously and asynchronously at a low frequency of 6 events/hour through a calcium‐dependent mechanism. ( 34 ) This has been proposed to cause propulsion of bile in the canaliculi. Again, the absence of any significant advection in the canalicular network indicates that in the absence of synchronized contractions along the CV–PV axis, merely mixing (rather than pumping) of canalicular contents may occur.…”

Section: Discussionmentioning

confidence: 99%

Intravital Dynamic and Correlative Imaging of Mouse Livers Reveals Diffusion‐Dominated Canalicular and Flow‐Augmented Ductular Bile Flux

et al. 2021

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Background and Aims Small‐molecule flux in tissue microdomains is essential for organ function, but knowledge of this process is scant due to the lack of suitable methods. We developed two independent techniques that allow the quantification of advection (flow) and diffusion in individual bile canaliculi and in interlobular bile ducts of intact livers in living mice, namely fluorescence loss after photoactivation and intravital arbitrary region image correlation spectroscopy. Approach and Results The results challenge the prevailing “mechano‐osmotic” theory of canalicular bile flow. After active transport across hepatocyte membranes, bile acids are transported in the canaliculi primarily by diffusion. Only in the interlobular ducts is diffusion augmented by regulatable advection. Photoactivation of fluorescein bis‐(5‐carboxymethoxy‐2‐nitrobenzyl)‐ether in entire lobules demonstrated the establishment of diffusive gradients in the bile canalicular network and the sink function of interlobular ducts. In contrast to the bile canalicular network, vectorial transport was detected and quantified in the mesh of interlobular bile ducts. Conclusions The liver consists of a diffusion‐dominated canalicular domain, where hepatocytes secrete small molecules and generate a concentration gradient and a flow‐augmented ductular domain, where regulated water influx creates unidirectional advection that augments the diffusive flux.

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Section: Discussionmentioning

confidence: 99%

Intravital Dynamic and Correlative Imaging of Mouse Livers Reveals Diffusion‐Dominated Canalicular and Flow‐Augmented Ductular Bile Flux

et al. 2021

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“…Moreover, bile acids, as hydrophobic molecules, are incorporated in phospholipid micelles, preventing them from exerting their full osmotic potential. On the other hand, recent work shows that canaliculi contract autonomously and asynchronously at a low frequency of 6 events/hour through a calcium-dependent mechanism ( 25 ) . This has been proposed to cause propulsion of bile in the canaliculi.…”

Section: Discussionmentioning

confidence: 99%

Intravital dynamic and correlative imaging reveals diffusion-dominated canalicular and flow-augmented ductular bile flux

Vartak

Guenther

Joly

et al. 2019

Preprint

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max 125 words):Small-molecule flux in tissue-microdomains is essential for organ function, but knowledge of this process is scant due to the lack of suitable methods applicable to live animals. We developed a methodology based on dynamic and correlative imaging for quantitative intravital flux analysis. Application to the liver, challenged the prevailing 'mechano-osmotic' theory of canalicular bile flow. After active transport across hepatocyte membranes bile salts are transported in the canaliculi primarily by diffusion. Only in the interlobular ducts, diffusion is augmented by regulatable advection. We corroborate these observations with in silico simulations and pan-species comparisons of lobule size. This study demonstrates a flux mechanism, where the energy invested in transmembrane transport entropically dissipates in a sub-micron scale vessel network.

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“…Canaliculi are known to contract autonomously and asynchronously at a low frequency of 6 events/hour through a calcium-dependent mechanism (34). This has been proposed to cause propulsion of bile in the canaliculi.…”

Section: Why Does the Excretion Of Bile Acids Into The Canaliculi Does Not Cause Any Measurable Advection?mentioning

confidence: 99%

Intravital dynamic and correlative imaging reveals diffusion‐dominated canalicular and flow‐augmented ductular bile flux

Vartak¹

2021

37. Jahrestagung Der Deutschen Arbeitsgemeinschaft Zum Studium Der Leber

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Actomyosin Contractility Drives Bile Regurgitation as an Early Homeostatic Response to Increased Biliary Pressure in Obstructive Cholestasis

Cited by 3 publications

References 45 publications

Intravital Dynamic and Correlative Imaging of Mouse Livers Reveals Diffusion‐Dominated Canalicular and Flow‐Augmented Ductular Bile Flux

Intravital Dynamic and Correlative Imaging of Mouse Livers Reveals Diffusion‐Dominated Canalicular and Flow‐Augmented Ductular Bile Flux

Intravital dynamic and correlative imaging reveals diffusion-dominated canalicular and flow-augmented ductular bile flux

Intravital dynamic and correlative imaging reveals diffusion‐dominated canalicular and flow‐augmented ductular bile flux

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