Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Anti-aging hormone Klotho inhibits renal fibrosis, cancer growth

14.04.2011
A natural hormone known to inhibit aging can also protect kidneys against renal fibrosis, UT Southwestern Medical Center researchers have demonstrated.

Scientists led by Dr. Makoto Kuro-o, associate professor of pathology, showed in mice that the anti-aging hormone Klotho suppressed both renal fibrosis ¡V a common complication of chronic kidney disease ¡V and the spread of cancer. The findings are available online in the Journal of Biological Chemistry.

More than 26 million people in the U.S. are affected by chronic kidney disease. Researchers say Klotho also helps patients with acute injury of the kidney that obstructs urine outflow or causes a drop in blood flow to the kidney. Nearly half of the patients in hospital intensive care units have some form of kidney injury due to drugs, surgery, bleeding or dehydration, said Dr. Kuro-o, the study's senior author who discovered Klotho more than a decade ago.

"Within a few days after injury, renal function can be completely gone," he said. "We show that Klotho injection in a drip infusion could be effective not only as an initial treatment for acute kidney injury, but also to prevent its progression into chronic kidney disease. This offers real hope for patients with renal disease."

The UT Southwestern researchers focused on mesenchymal cells: multipotent cells that can differentiate into a variety of cell types. These are essential for development and growth, but when the cells are out of balance, they can morph into a pathological form that causes fibrosis (toughening of the tissue layers) and metastasis in cancer cells, said Dr. Kuro-o.

Scientists involved in this study also found that Klotho prevents cancer migration and metastasis. In the study, they blocked a ureter to cause renal fibrosis or introduced human cancer cells in laboratory mice. Secreted Klotho was effective in blocking three signaling pathways ¡V TGF-ƒÒ1, Wnt and IGF-1 ¡V that can cause tissue fibrosis or cancer metastasis.

The researchers reported for the first time that Klotho binds to the cells' transforming growth factor receptor and inhibits signaling required for epithelial-to-mesenchymal transition (EMT), a "master switch" that causes cells to morph into a more pliable form. EMT cancer cells can squeeze into surrounding tissue and eventually into the bloodstream, leading to metastatic spreading of cancer.

"This is further evidence that Klotho is an understudied tumor-suppressor and really quite important because it's secreted and flows through the body," said Dr. David Boothman, professor of radiation oncology and pharmacology, associate director for translational research and an author of the study. "It could be a major surveillance mechanism for blocking tumor formation and progression."

Other UT Southwestern researchers involved in the study were lead author Dr. Shigehiro Doi, former postdoctoral researcher in pathology now at Hiroshima University in Japan; co-lead author Dr. Yonglong Zou, research associate in the Harold C. Simmons Comprehensive Cancer Center; Dr. Osamu Togao, postdoctoral researcher in the Advanced Imaging Research Center (AIRC); Johanne Pastor, senior research associate in pathology; Dr. George John, instructor of pathology; Lei Wang, research assistant in pathology; Dr. Kazuhiro Shizaki, instructor of pathology; and Dr. Masaya Takahashi, associate professor of radiology and in the AIRC.

Funding for the study was provided in part by grants from the National Institutes of Health, the Department of Energy, Genzyme Corp. and Philips Japan.

Visit www.utsouthwestern.org/cancer to learn more about UT Southwestern's clinical services in cancer. For more about clinical services in urology at UT Southwestern, visit www.utsouthwestern.org/urology .

This news release is available on our World Wide Web home page at http://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 Staying in Shape
16.08.2018 | Max-Planck-Institut für molekulare Zellbiologie und Genetik

nachricht Chips, light and coding moves the front line in beating bacteria
16.08.2018 | Okinawa Institute of Science and Technology (OIST) Graduate University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Staying in Shape

16.08.2018 | Life Sciences

Diving robots find Antarctic seas exhale surprising amounts of carbon dioxide in winter

16.08.2018 | Earth Sciences

Protein droplets keep neurons at the ready and immune system in balance

16.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>