Using vitamin A to target the cells that cause liver cirrhosis may improve the treatment of the disease, according to research reported online in Nature Biotechnology.
Cirrhosis, which affects hundreds of millions of people worldwide, is a scarring response to liver damage, which is most commonly inflicted by hepatitis infection, alcohol abuse or nutritional deficiencies. It occurs when specialized liver cells called stellate cells are triggered to produce collagen, the fibrous material that toughens skin and tendons. There are no approved antifibrotic therapies, partly due to the difficulty in specifically targeting collagen-producing cells to avoid unwanted side effects on healthy tissue.
Yoshiro Niitsu and colleagues exploit two properties of liver stellate cells -- their ability to take up vitamin A and to make collagen. First, they designed small interfering RNA molecules (siRNAs) that block a key protein in collagen synthesis. Then, by packaging the siRNAs in carriers coated with vitamin A, they tricked the stellate cells into letting in the inhibitor, which shut down collagen secretion.
The treatment rescued rats from cirrhosis induced by three different approaches. As relatives of liver stellate cells contribute to fibrosis in organs, such as the pancreas and kidney, this type of siRNA therapy might be extended to reverse other fibrotic conditions.
Yoshiro Niitsu (Sapporo Medical University School of Medicine, Hokkaido, Japan)
Abstract available online.
(C) Nature Biotechnology press release.
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