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Sunshine hormone, vitamin D, may offer hope for treating liver fibrosis

liver tissue

This image shows mouse liver tissue with fibrosis (red), a type of scarring caused by chronic liver diseases and injuries. Salk researchers found that a drug already approved by the FDA for the treatment of psoriasis deactivates the switch governing the fibrotic response in mouse liver cells, suggesting a potential new therapy for fibrotic diseases in humans.

There are currently no effective drugs for liver fibrosis, the accumulation of tough, fibrous scar tissue that occurs in most types of chronic liver diseases. Existing therapeutic approaches, which treat the symptoms of liver disease, do not stop liver fibrosis from progressing.

Researchers led by Ronald M. Evans, however, have recently discovered that a synthetic, hormonally active form of vitamin D, calcipotriol (a drug already approved by the FDA to treat psoriasis), deactivates the switch governing the fibrotic response in mouse liver cells, suggesting a potential new therapy for fibrotic diseases in humans. Their study, which was reported in Cell, focused on a star-shaped "stellate" cell in the liver that serves as a beacon for damage. When called into action, stellate cells produce fibrotic proteins in an attempt to heal an injury. Under chronic stress, localized fibrosis expands, eventually leading to cirrhosis, increased risk of liver cancer and even the need for a liver transplant.

The Evans lab discovered a genetic switch through which vitamin D–related ligands such as calcitriol can put the brakes on fibrosis. "Preclinical results suggest the 'vitamin D brake' is highly efficacious and led us to believe that the time is right to consider a trial in the context of chronic liver disease," says Evans.

Previous studies have shown a physiologic role for vitamin D in liver function, says Ning Ding, a research associate in Evans's group, but he notes that it was the discovery of high levels of vitamin D receptor (VDR) in the stellate cell that led the team to consider it as a possible off switch for liver fibrosis.

In liver diseases where the underlying cause cannot be cured, progression to cirrhosis is currently inevitable in some people. What Evans's team has discovered is that by acting on the genome, VDR can simultaneously defend against multiple fibrotic activators. This is important because many different pro-fibrotic signaling pathways converge on the genome to affect their fibrotic response. Their discovery suggests a potentially safer, more effective strategy capable of neutralizing these multiple convergent fibrotic triggers.