Navigation Links
Tumor suppressor may attenuate fibrotic disease

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
Cell Press

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:
(Date:11/27/2015)... ... November 27, 2015 , ... Lizzie’s Lice Pickers just announced a ... customers 10% off of their purchase of lice treatment product. In addition, customers will ... to a company spokesperson. “Finding lice is a sure way to ruin the holidays, ...
(Date:11/27/2015)... ... November 27, 2015 , ... MPWH, the No.1 Herpes-only dating community in the world, revealed that ... ). More than 3.7 billion people under the age of 50 – or 67% ... WHO's first global estimates of HSV-1 infection . , "The data shocks us highly!" ...
(Date:11/27/2015)... ... 2015 , ... A simply groundbreaking television series, "Voices in America", which is ... an array of issues that are presently affecting Americans. Dedicated to providing the world ... is changing the subjects consumers focus on, one episode at a time. , ...
(Date:11/27/2015)... Los Angeles, CA (PRWEB) , ... November 27, 2015 , ... ... the Commission on Accreditation of Allied Health Education Programs (CAAHEP) awarded accreditation to its ... exclusive list of CAAHEP accredited colleges, as only one of twelve colleges and universities ...
(Date:11/27/2015)... ... November 27, 2015 , ... Avid collector, Andrew Hawley from ... boxing style concert posters. This is one of Joplin's most famous and beautiful concert ... the University of Michigan in Ann Arbor. The According to Hawley, "It is hard ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... 3D bioprinting market is expected ... new report by Grand View Research Inc. Rising prevalence of ... kidney transplantation is expected to boost the market growth, as ... transplantation. --> 3D bioprinting market is expected ... new report by Grand View Research Inc. Rising prevalence of ...
(Date:11/26/2015)... STOCKHOLM , November 26, 2015 /PRNewswire/ ... --> Juntendo universitetssjukhus ser potential att ... av magnetresonansbilder (MR-bilder) för patienter med ... tecknat ett forskningsavtal med SyntheticMR AB för ... kliniska forskningsprojekt på sjukhuset. Med SyMRI kan ...
(Date:11/26/2015)... , Nov. 26, 2015 Research and ... of the "2016 Future Horizons and Growth ... Market: Supplier Shares, Country Segment Forecasts, Competitive Intelligence, ... --> --> ... of the Italian therapeutic drug monitoring market, including ...
Breaking Medicine Technology: