Nav: Home

Talking receptors may affect relaxin at work

September 11, 2019

Fibrosis, the damaging build-up of hardened or scarred tissue in the body, is a hallmark of various diseases and can lead to the dysfunction and failure of organs such as the heart and kidney. Fibrosis-related diseases in various organs contribute to around 45 per cent of deaths in developed countries.

A Monash Biomedicine Discovery Institute (BDI) researcher leading a team investigating the promising anti-fibrotic effects of a drug version of the hormone, relaxin, has discovered that the receptor through which it mediates its therapeutic actions can communicate and/or interact with other receptors in cells that contribute to fibrosis progression. Receptors are protein structures that transmit signals to other parts of the body when triggered by a stimulus.

The study, led by Associate Professor Chrishan Samuel and published in the Journal of the American Society of Nephrology today, suggests the ability of receptors to 'talk' to each other may affect the way relaxin (and other drugs that act through the receptors) work. It may have implications for the design of clinical trials involving relaxin and its concomitant use with other drugs that act on these receptors.

Associate Professor Samuel said the paper describes for the first time the communication between three receptors that exist on myofibroblasts, the cellular basis of progressive fibrosis. The receptors investigated were: the relaxin family peptide receptor 1 (RXFP1, which relaxin acts through to reduce tissue fibrosis and related dysfunction); the angiotensin II type 1 (AT1) receptor, which is targeted by clinically-used angiotensin receptor blockers to treat high blood pressure-induced organ damage; and the angiotensin II type 2 (AT2) receptor, which can also facilitate the reduction of tissue fibrosis by compounds that stimulate its activity.

"We've shown that because these receptors have the ability to communicate, they have the ability to either promote or negate the actions of various drugs that act on each receptor. For example, our findings suggest that the effects of relaxin may be compromised as a treatment for heart failure when administered to patients who are already receiving angiotensin receptor blockers as frontline treatments."

The communication between the receptors resulted in the anti-fibrotic effects of relaxin being indirectly abolished by compounds that blocked the activity of the AT1 receptor or AT2 receptor. Likewise, the anti-fibrotic effects of a drug that acted through the AT2 receptor were indirectly abrogated by compounds that blocked the activity of RXFP1 or the AT1 receptor in myofibroblasts.

Relaxin, a hormone that is also naturally produced during pregnancy, plays several roles in facilitating childbirth by reducing the rigidity of the pelvic ligaments. It has been well studied for its organ-protective actions at the pre-clinical level, but has not yet been approved as an anti-fibrotic agent.

"What we need to do now is better understand how these receptors communicate, not just in myofibroblasts, but in other cells in which they are co-localised. With an improved understanding of how these receptors interact, they may represent a previously unrecognised target for treating organ fibrosis."
-end-
The study was a collaboration between Monash BDI and institutions including the Monash Institute of Pharmaceutical Sciences, Florey Institute of Neuroscience and Mental Health, and the Harry Perkins Institute of Medical Research and Centre for Medical Research, University of Western Australia.

Read the full paper in the Journal of the American Society of Nephrology titled Evidence of AT1R-AT2R-RXFP1 Functional Crosstalk in Myofibroblasts and its Impact on the Therapeutic Targeting of Renal and Cardiac Fibrosis.

About the Monash Biomedicine Discovery Institute

Committed to making the discoveries that will relieve the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.

Monash University

Related Heart Failure Articles:

New hope for treating heart failure
Heart failure patients who are getting by on existing drug therapies can look forward to a far more effective medicine in the next five years or so, thanks to University of Alberta researchers.
Activated T-cells drive post-heart attack heart failure
Chronic inflammation after a heart attack can promote heart failure and death.
ICU care for COPD, heart failure and heart attack may not be better
Does a stay in the intensive care unit give patients a better chance of surviving a chronic obstructive pulmonary disease (COPD) or heart failure flare-up or even a heart attack, compared with care in another type of hospital unit?
Tissue engineering advance reduces heart failure in model of heart attack
Researchers have grown heart tissue by seeding a mix of human cells onto a 1-micron-resolution scaffold made with a 3-D printer.
Smoking may lead to heart failure by thickening the heart wall
Smokers without obvious signs of heart disease were more likely than nonsmokers and former smokers to have thickened heart walls and reduced heart pumping ability.
More Heart Failure News and Heart Failure Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Erasing The Stigma
Many of us either cope with mental illness or know someone who does. But we still have a hard time talking about it. This hour, TED speakers explore ways to push past — and even erase — the stigma. Guests include musician and comedian Jordan Raskopoulos, neuroscientist and psychiatrist Thomas Insel, psychiatrist Dixon Chibanda, anxiety and depression researcher Olivia Remes, and entrepreneur Sangu Delle.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...