AsianScientist (July 6, 2017) – In a study published in the Journal of Hepatology, researchers from Singapore have discovered how liver cells remove excess bile when the bile ducts are blocked. These findings could lead to new treatments for biliary atresia, a rare, life-threatening liver disease that affects infants, particularly those of Asian descent.
In babies suffering from biliary atresia, bile accumulates in the biliary ducts. Without surgical intervention, long-term liver damage or cirrhosis will occur. To date, there are no drugs available to treat biliary atresia.
To investigate how the liver responds to bile accumulation, a multi-disciplinary team of researchers from the Mechanobiology Institute, Singapore at the National University of Singapore, the Institute of Bioengineering and Nanotechnology of the Agency for Science, Technology and Research, and BioSyM at the Singapore-MIT Alliance for Research and Technology used an artificial culture system which allowed the easy manipulation of cultured liver cells.
Inside this culture system, living tubes that mimic the structure of the biliary tract within actual livers developed. The researchers then used high-end imaging techniques to visualize the dynamics of the tubes when they became obstructed.
The team noticed that as the bile accumulated behind the blockage, the tube began to swell or bulge, putting pressure on the cells that make up the wall of the tube. As pressure builds up, the network of protein cables or filaments inside liver cell ruptures and is not repaired.
Although the bile cannot simply pass through the membrane, it pushes the membrane into the cell through the gap in the ruptured actin cortex. A bubble-like vesicle thus forms inside the cell, allowing bile to be transported through the cel, and away from the site where it had accumulated.
It is hoped that this mechanism may one day be therapeutically targeted to improve the prognosis for infants with biliary atresia. By increasing the rate of vesicle formation using drugs, bile may be eliminated more effectively from the blocked duct, thus avoiding long-term liver damage and increasing the effectiveness of surgical intervention.
The article can be found at: Gupta et al. (2017) Actomyosin Contractility Drives Bile Regurgitation as an Early Response During Obstructive Cholestasis.
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Source: National University of Singapore.
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