Navigation Links
Tumor suppressor may attenuate fibrotic disease
Date:2/17/2009

New research reveals a critical cellular signaling pathway that is responsible for generating excess connective tissue in multiple organs, similar to what is seen in human patients with scleroderma. The study, published by Cell Press in the February issue of the journal Developmental Cell, also reveals an intriguing but unexpected regulatory role for a tumor suppressor gene in fibrotic disease.

Platelet derived growth factors (PDGF) regulate the proliferation, survival, migration and differentiation of cells and play a critical role during embryonic development. However, the consequences of excess PDGF signaling are not very well understood.

"Aberrant PDGF signaling has been implicated in diverse fibrotic conditions where connective tissue cells called fibroblasts proliferate and deposit excessive connective tissue, leading to progressive scarring and organ dysfunction," says senior study author, Dr. Philippe Soriano from the Mount Sinai School of Medicine in New York."For example, human scleroderma patients, who characteristically exhibit widespread fibrosis, possess antibodies that activate PDGF receptors."

Dr. Soriano and Dr. Lorin E. Olson, who conducted this work initially at the Fred Hutchinson Cancer Research Center in Seattle and then pursued it at Mount Sinai, developed a mouse model in which they could selectively activate the PDGF receptor alpha (PDGFR?) during embryonic development and in adult animals.

The researchers found that elevated PDGFR? signaling led to aberrant overgrowth of connective tissue. In adults, this led to a progressive fibrosis in multiple organs. Interestingly, loss of the tumor suppressor Ink4a/Arf dramatically accelerated the development of fibrotic lesions. This finding suggests that cells may attenuate the effects of PDGFR? signaling through an Ink4a/Arf-dependent mechanism.

The study provides insight into the signaling pathways involved in connective tissue disease and highlights a new role for tumor-suppressors in the regulation of fibrotic conditions. "Our findings provide direct evidence that increased PDGFR? signaling can be sufficient to drive systemic connective tissue disease in organ systems that are relevant to human scleroderma," concludes Dr. Soriano. "The work also establishes an excellent animal model for testing novel therapeutic approaches for blocking aberrant PDGFR? signaling in human disease."


'/>"/>

Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

Related medicine news :

1. Estrogen found to increase growth of the most common childhood brain tumor
2. Blocking protein leads to fewer, smaller skin cancer tumors
3. Dosing Begins in Phase 1 Clinical Study Evaluating NKTR-105 in Cancer Patients With Refractory Solid Tumors
4. Immune Cells Shrink Tumors in Mice
5. Normalizing tumor vessels leaves cancer more benign
6. Biking for Fun, Sport, and Brain Tumor Awareness
7. Innovative method to starve tumors
8. Levels of Circulating Tumor Cells Could Predict Prostate Cancer Outcome
9. Researchers Identify Novel Mechanism That Make Cancer Tumors Grow
10. Radiofrequency treatment better than ethanol injection for small liver tumors
11. Surgical technique in Spain enables extirpation of benign tumors of the pancreas
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/27/2016)... ... May 27, 2016 , ... Beleza Medspa has initiated a new ... This is the first time that Coolsculpting is being used for for more than ... to ensure they meet the prescribed body-fat standard, measured by the circumference-based tape method. ...
(Date:5/27/2016)... (PRWEB) , ... May 27, 2016 , ... Aimed at ... human interest stories, which come courtesy of leaders in the nursing and health care ... from leading advocates and associations—namely Abilene Christian University. , As the nursing industry ...
(Date:5/27/2016)... ... May 27, 2016 , ... ... the pharmaceutical, medical and food industries. Aside from its GMP accreditation, Validation Center ... proof of successfully certified products, services and staff. , Validation Center is ISO17025 ...
(Date:5/26/2016)... ... May 26, 2016 , ... There are many ways to cook ... Council (NHDSC) suggests that Americans prefer their dogs straight off the grill. Of the ... is their favorite way to cook a hot dog, far outpacing other cooking methods ...
(Date:5/26/2016)... ... May 26, 2016 , ... Cabot ... of defective respirators, according to court documents and SEC filings. A jury ... Becky Tyler v. American Optical Corporation, Case No. BC588866, Los Angeles County, California. ...
Breaking Medicine News(10 mins):
(Date:5/24/2016)... -- Cirujanos holandeses han puesto en marcha ... a compartir sus mejores prácticas por el mundo y ... de Europa, África, Asia y ... que combina la transmisión en vivo con mensajería instantánea ... Educación   "Imagine un médico de Medicines sans ...
(Date:5/24/2016)... -- Diana Russell suffers from a form of rheumatoid arthritis ... This disease has put her in a wheelchair, and ... to leave her home.  Because of the size and ... wheelchair.  So if there is a family function, the ... to wait for the bus. Photo - ...
(Date:5/24/2016)... N.J. , May 24, 2016 ... oncology drug development company, today provided an update ... dose escalating clinical trial combining GEN-1, the Company,s ... the treatment of newly-diagnosed patients with advanced ovarian ... interval debulking surgery.  GEN-1 is an IL-12 DNA ...
Breaking Medicine Technology: