Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


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

Salk findings suggest vitamin D therapy could be a powerful weapon in the fight against liver fibrosis

Liver fibrosis results from an excessive accumulation of tough, fibrous scar tissue and occurs in most types of chronic liver diseases. In industrialized countries, the main causes of liver injury leading to fibrosis include chronic hepatitis virus infection, excess alcohol consumption and, increasingly, nonalcoholic steatohepatitis (NASH).

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.

Credit: Image: Courtesy of the Salk Institute for Biological Studies

Now, in a new study published in the journal Cell, scientists at the Salk Institute for Biological Studies have discovered that a synthetic form of vitamin D, calcipotriol (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.

"Because there are currently no effective drugs for liver fibrosis, we believe our findings would open a new door for treatment," says senior author Ronald M. Evans, a professor in Salk's Gene Expression Laboratory and lead researcher in the Institute's new Helmsley Center for Genomic Medicine.

The Salk study 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, however, localized fibrosis expands, eventually leading to cirrhosis, increased risk of liver cancer, and the need for a liver transplant in advanced cases.

The Evans lab discovered a genetic switch through which vitamin D-related ligands such as calcitriol, a hormonally active form of the vitamin, 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, a Howard Hughes Medical Institute Investigator and holder of the March of Dimes Chair in Molecular and Developmental Biology.

Previous studies have shown a physiologic role for vitamin D in liver function, but "it was our discovery of high levels of vitamin D receptor (VDR) in the stellate cell that led us to consider it as a possible off switch for liver fibrosis," says lead author Ning Ding, a research associate in the Gene Expression Laboratory.

"Current therapeutic approaches, which treat the symptoms of liver disease, don't stop liver fibrosis from progressing," says Michael Downes, a senior staff scientist in the Gene Expression Laboratory and co-corresponding author on the paper. "In liver diseases where the underlying cause cannot be cured, progression to cirrhosis is currently inevitable in some people. What we have 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."

The Salk discovery that calcipotriol counters the fibrotic response in stellate cells illuminates a potentially safer, more effective strategy capable of neutralizing multiple convergent fibrotic triggers.

The Salk scientists say that clinical trials of the vitamin D analog for the treatment of liver fibrosis are being planned. The synthetic vitamin D analog is better than natural vitamin D, they say, for a couple of reasons. First, natural vitamin D, which is found in small amounts in a few foods and produced in the body by exposure to sunlight, degrades quickly, while synthetic versions of vitamin D are less susceptible to breakdown. Second, too much natural vitamin D can cause hypercalcemia, or elevated calcium in the blood, which can lead to nausea and vomiting, frequent urination, muscle weakness and joint aches and pain. The synthetic vitamin D analog, on the other hand, produces a strong response without adding calcium to the blood.

In addition, the researchers say this new model for treating liver fibrosis may also be helpful in treating other diseases with a fibrotic component, including those of the lung, kidney and pancreas.

Other researchers on the study were Ruth T. Yu, Mara H. Sherman, Mathias Leblanc, Mingxiao He, Annette R. Atkins and Grant D. Barish, from the Salk Institute; Nanthakumar Subramaniam, Caroline Wilson, Renuka Rao, Sally Coulter and Christopher Liddle, of the University of Sydney (Australia); and Sue L. Lau , Christopher Scott and Jenny E. Gunton, of the Garvan Insitute for Medical Research (Australia).

The work was supported by grants from the National Institutes of Health, the Howard Hughes Medical Institute, the National Health and Medical Research Council of Australia, the Genentech Foundation,the Leona M. and Harry B. Helmsley Charitable Trust, the Samuel Waxman Cancer Research Foundation, Stand Up to Cancer and Ipsen/Biomeasure.

About the Salk Institute for Biological Studies:

The Salk Institute for Biological Studies is one of the world's preeminent basic research institutions, where internationally renowned faculty probe fundamental life science questions in a unique, collaborative, and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer's, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines.

Faculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, M.D., the Institute is an independent nonprofit organization and architectural landmark.

Andy Hoang | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht Inflammation Triggers Unsustainable Immune Response to Chronic Viral Infection
24.10.2016 | Universität Basel

nachricht Resolving the mystery of preeclampsia
21.10.2016 | Universitätsklinikum Magdeburg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Oasis of life in the ice-covered central Arctic

24.10.2016 | Earth Sciences

‘Farming’ bacteria to boost growth in the oceans

24.10.2016 | Life Sciences

Light-driven atomic rotations excite magnetic waves

24.10.2016 | Physics and Astronomy

More VideoLinks >>>