Featured Research

from universities, journals, and other organizations

Protein breakdown contributes to pelvic organ prolapse

Date:
May 24, 2011
Source:
UT Southwestern Medical Center
Summary:
A gynecologist and a molecular biologist have shown 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.

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.


Story Source:

The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Madhusudhan Budatha, Shayzreen Roshanravan, Qian Zheng, Cecilia Weislander, Shelby L. Chapman, Elaine C. Davis, Barry Starcher, R. Ann Word, Hiromi Yanagisawa. Extracellular matrix proteases contribute to progression of pelvic organ prolapse in mice and humans. Journal of Clinical Investigation, 2011; 121 (5): 2048 DOI: 10.1172/JCI45636

Cite This Page:

UT Southwestern Medical Center. "Protein breakdown contributes to pelvic organ prolapse." ScienceDaily. ScienceDaily, 24 May 2011. <www.sciencedaily.com/releases/2011/05/110524070316.htm>.
UT Southwestern Medical Center. (2011, May 24). Protein breakdown contributes to pelvic organ prolapse. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2011/05/110524070316.htm
UT Southwestern Medical Center. "Protein breakdown contributes to pelvic organ prolapse." ScienceDaily. www.sciencedaily.com/releases/2011/05/110524070316.htm (accessed July 23, 2014).

Share This




More Health & Medicine News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Scientists Find New Way To Make Human Platelets

Scientists Find New Way To Make Human Platelets

Newsy (July 22, 2014) Boston scientists have discovered a new way to create fully functioning human platelets using a bioreactor and human stem cells. Video provided by Newsy
Powered by NewsLook.com
Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins