Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UT Southwestern researchers find protein breakdown contributes to pelvic organ prolapse

24.05.2011
A gynecologist and a molecular biologist at UT Southwestern Medical Center have collaborated to show for the first time that pelvic organ prolapse – a condition in which the uterus, bladder or vagina protrude from the body – is caused by a combination of a loss of elasticity and a breakdown of proteins in the vaginal wall.

Pelvic organ prolapse affects many women older than 50 years of age. Besides creating pelvic pressure, prolapse can lead to other pelvic-floor disorders such as urinary and fecal incontinence, and can affect sexual function.

"We found that the protein fibulin-5, which until now simply has been known to be important in generating elastic fibers, actually blocks the enzymes that degrade proteins that support the vaginal wall structure," said Dr. R. Ann Word, professor of obstetrics and gynecology and a co-senior author of the study in May edition of the Journal of Clinical Investigation. "The elastic fibers do play a role, but it's also the enzymes that degrade the matrix that break down both collagen and elastin over time."

More than 225,000 inpatient surgical procedures for pelvic organ prolapse are performed each year in the U.S. at an estimated cost of more than $1 billion. But surgery alone is not always effective in the long run; nearly 30 percent of women report continued problems over a five-year follow-up period because the underlying problem of matrix support has not been corrected. There are no current therapies to prevent the progression of prolapse.

Age and vaginal delivery are the two most common risk factors for prolapse; injury to the vaginal wall may occur during childbirth but prolapse often doesn't occur until decades later. Obesity and menopause are also contributing factors.

"We still don't understand why patient A has a terrible delivery, with a large baby, but she never gets prolapse. And then we see patients who are 28 with no children, and they're already starting to have problems. So we know genetic and environmental factors contribute to this," Dr. Word said.

Using mice, researchers tested how fibulin-5, a protein that is essential for elastic fiber assembly, regulated the activity of matrix metalloprotease-9 (MMP-9), a group of enzymes that break down the matrix of collagen and elastic fibers, leading to a loss of the structural support of the vaginal wall.

Researchers used a fibulin-5 deficient rodent model and a new domain-specific mutant of fibulin-5 to demonstrate that fibulin-5-mediated elastogenesis (development of elastic fibers) is essential to support the pelvic organs. They also showed that prolapse of the vaginal wall requires an increase in MMP-9, but that fibulin-5 inhibits activation of this protease in a tissue-specific manner.

"Matrix assembly of the vaginal wall is a very complicated process," said Dr. Hiromi Yanagisawa, assistant professor of molecular biology and the study's other co-senior author. "We need to decode what is necessary in this process, but degrading enzymes are the main therapeutic focus."

Dr. Word said, "The bottom line is the whole matrix is maintained by a balance between synthesis and degradation. Our goal is to optimize pelvic organ support and target these proteases that degrade the matrix."

Other UT Southwestern researchers involved in the study were Dr. Madhusudhan Budatha, postdoctoral researcher of molecular biology and lead author; Dr. Quin Zheng, former postdoctoral researcher of molecular biology; Dr. Shayzreen Roshanravan and Dr. Cecilia Weislander, former postdoctoral researchers of obstetrics and gynecology; and Shelby Chapman, senior research associate of molecular biology. Scientists from UT Health Center in Tyler and McGill University in Montreal also participated.

The study was supported by grants from the National Institutes of Health, the American Heart Association and the Welch Foundation.

Visit http://www.utsouthwestern.org/obgyn to learn more about clinical services for obstetrics and gynecology at UT Southwestern.

This news release is available on our World Wide Web home page at www.utsouthwestern.edu/home/news/index.html

To automatically receive news releases from UT Southwestern via email, subscribe at www.utsouthwestern.edu/receivenews

Robin Russell | EurekAlert!
Further information:
http://www.utsouthwestern.edu

More articles from Life Sciences:

nachricht Genome Duplication Drives Evolution of Species
25.09.2018 | Universität Zürich

nachricht Why it doesn’t get dark when you blink
25.09.2018 | Deutsches Primatenzentrum GmbH - Leibniz-Institut für Primatenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Hygiene at your fingertips with the new CleanHand Network

The Fraunhofer FEP has been involved in developing processes and equipment for cleaning, sterilization, and surface modification for decades. The CleanHand Network for development of systems and technologies to clean surfaces, materials, and objects was established in May 2018 to bundle the expertise of many partnering organizations. As a partner in the CleanHand Network, Fraunhofer FEP will present the Network and current research topics of the Institute in the field of hygiene and cleaning at the parts2clean trade fair, October 23-25, 2018 in Stuttgart, at the booth of the Fraunhofer Cleaning Technology Alliance (Hall 5, Booth C31).

Test reports and studies on the cleanliness of European motorway rest areas, hotel beds, and outdoor pools increasingly appear in the press, especially during...

Im Focus: Scientists present new observations to understand the phase transition in quantum chromodynamics

The building blocks of matter in our universe were formed in the first 10 microseconds of its existence, according to the currently accepted scientific picture. After the Big Bang about 13.7 billion years ago, matter consisted mainly of quarks and gluons, two types of elementary particles whose interactions are governed by quantum chromodynamics (QCD), the theory of strong interaction. In the early universe, these particles moved (nearly) freely in a quark-gluon plasma.

This is a joint press release of University Muenster and Heidelberg as well as the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt.

Then, in a phase transition, they combined and formed hadrons, among them the building blocks of atomic nuclei, protons and neutrons. In the current issue of...

Im Focus: Patented nanostructure for solar cells: Rough optics, smooth surface

Thin-film solar cells made of crystalline silicon are inexpensive and achieve efficiencies of a good 14 percent. However, they could do even better if their shiny surfaces reflected less light. A team led by Prof. Christiane Becker from the Helmholtz-Zentrum Berlin (HZB) has now patented a sophisticated new solution to this problem.

"It is not enough simply to bring more light into the cell," says Christiane Becker. Such surface structures can even ultimately reduce the efficiency by...

Im Focus: New soft coral species discovered in Panama

A study in the journal Bulletin of Marine Science describes a new, blood-red species of octocoral found in Panama. The species in the genus Thesea was discovered in the threatened low-light reef environment on Hannibal Bank, 60 kilometers off mainland Pacific Panama, by researchers at the Smithsonian Tropical Research Institute in Panama (STRI) and the Centro de Investigación en Ciencias del Mar y Limnología (CIMAR) at the University of Costa Rica.

Scientists established the new species, Thesea dalioi, by comparing its physical traits, such as branch thickness and the bright red colony color, with the...

Im Focus: New devices based on rust could reduce excess heat in computers

Physicists explore long-distance information transmission in antiferromagnetic iron oxide

Scientists have succeeded in observing the first long-distance transfer of information in a magnetic group of materials known as antiferromagnets.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

"Boston calling": TU Berlin and the Weizenbaum Institute organize a conference in USA

21.09.2018 | Event News

One of the world’s most prominent strategic forums for global health held in Berlin in October 2018

03.09.2018 | Event News

4th Intelligent Materials - European Symposium on Intelligent Materials

27.08.2018 | Event News

 
Latest News

Why it doesn’t get dark when you blink

25.09.2018 | Life Sciences

Genome Duplication Drives Evolution of Species

25.09.2018 | Life Sciences

Desert ants have an amazing odor memory

25.09.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>