Adaptive regulation of bile salt transporters in kidney and liver in obstructive cholestasis in the rat

Area of Science:

• Hepatology
• Nephrology
• Molecular Biology

Background:

• Cholestasis leads to adaptive regulation of bile salt transporters in liver cells.
• The impact of cholestasis on bile salt transporters in extrahepatic tissues, like the kidney, remains unclear.
• Kidney adaptations may play a role in excreting bile salts during obstructive cholestasis.

Purpose of the Study:

• To investigate adaptive changes in bile salt transporter expression in the kidney during cholestasis.
• To determine if the kidney facilitates bile salt excretion in response to bile duct obstruction.

Main Methods:

• Rats underwent common bile duct ligation to induce cholestasis.
• RNA and protein expression of bile salt transporters were analyzed in liver and kidney tissues.
• Sodium-dependent bile salt transport and transporter protein levels were measured in kidney brush border membrane vesicles.

Main Results:

• Serum bile salts initially increased then decreased, while urinary bile salt excretion rose progressively after bile duct ligation.
• Ileal sodium-dependent bile salt transporter expression increased in the liver but decreased in the kidney.
• Multidrug resistance-associated protein 2 expression in the kidney doubled, indicating altered transport mechanisms.

Conclusions:

• Common bile duct obstruction induces adaptive molecular changes in kidney bile salt transporters.
• These renal adaptations may contribute to extrahepatic bile salt excretion during cholestasis.
• The kidney plays a role in managing bile salt homeostasis during cholestasis.