Navigation Links
Tweaking gene expression to repair lungs
Date:2/25/2013

PHILADELPHIA Lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) are on the rise, according to the American Lung Association and the National Institutes of Health.

These ailments are chronic, affect the small airways of the lung, and are thought to involve an injury-repair cycle that leads to the breakdown of normal airway structure and function. For now, drugs for COPD treat only the symptoms.

"A healthy lung has some capacity to regenerate itself like the liver," notes Ed Morrisey, Ph.D., professor of Medicine and Cell and Developmental Biology and the scientific director of the Penn Institute for Regenerative Medicine in the Perelman School of Medicine, University of Pennsylvania. "In COPD, these reparative mechanisms fail."

Morrisey is looking at how epigenetics controls lung repair and regeneration. Epigenetics involves chemical modifications to DNA and its supporting proteins that affect gene expression. Previous studies found that smokers with COPD had the most significant decrease in one of the enzymes controlling these modifications, called HDAC2.

"HDAC therapies may be useful for COPD, as well as other airway diseases," he explains. "The levels of HDAC2 expression and its activity are greatly reduced in COPD patients. We believe that decreased HDAC activity may impair the ability of the lung epithelium to regenerate."

Using genetic and pharmacological approaches, they showed that development of progenitor cells in the lung is specifically regulated by the combined function of two highly related HDACs, HDAC/1 and /2. Morrisey and colleagues published their findings in this week's issue of Developmental Cell.

By studying how HDAC activity, as well as other epigenetic regulators, controls lung development and regeneration, they hope to develop new therapies to alleviate the unmet needs of patients with asthma and COPD.

HDAC1/2 deficiency leads to a loss of expression of the key transcription factor, a protein called Sox2, which in turn leads to a block in airway epithelial cell development. This is affected in part by deactivating a repressor of expression (derepressing) of two other proteins, Bmp4 and the tumor suppressor Rb1 - targets of HDAC1/2.

In the adult lung, loss of HDAC1/2 leads primarily to increased expression of inhibitors of cell proliferation including the proteins Rb1, p16, and p21. This results in decreased epithelial proliferation in lung injury and inhibition of regeneration.

Together, these data support a critical role for HDAC-mediated mechanisms in regulating both development and regeneration of lung tissue. Since HDAC inhibitors and activators are currently in clinical trials for other diseases, including cancer, such compounds could be tested in the future for efficacy in COPD, acute lung injury, and other lung diseases that involve defective repair and regeneration, says Morrisey.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

Related medicine news :

1. Synthetic circuit allows dialing gene expression up or down in human cells
2. Gene expression improves the definition of a breast cancer subtype
3. Gene expression test identifies low-risk thyroid nodules
4. Overexpression of proteins 14-3-3 related to chemotherapy resistance
5. Control of gene expression: Histone occupancy in your genome
6. Changes in gene expression may help explain high blood pressure in pregnancy
7. Injected Hydrogel May Help Repair Failing Hearts
8. US Drug Watchdog Now Urges Victims Of A Transvaginal Mesh, Tape Or Sling Repair Surgery That Failed To Call Them For The Names Of The Best Possible Women Lawyers
9. US Drug Watchdog Now Urges Victims of a Transvaginal Mesh Product Failure to Call Them for the Names of Top Women Attorneys - Especially if They had a Failed Repair Surgery
10. Mussel-inspired glue for surgical repair and cancer drug delivery
11. US Drug Watchdog Now Urges Transvaginal Mesh Failure Victims Who Have Had an Unsuccessful Repair Surgery to Call Them for the Names and Contacts of the Best Women Lawyers
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Tweaking gene expression to repair lungs
(Date:5/4/2016)... NY (PRWEB) , ... May 04, 2016 , ... ... non-profit organization devoted exclusively to funding innovative lymphoma research and serving the lymphoma ... – is set to return to the esteemed Quaker Ridge Golf Club in ...
(Date:5/4/2016)... York, NY (PRWEB) , ... May 04, 2016 ... ... leading private owners, developers and operators of commercial real estate proudly announced that ... 2015 Heart Health initiative. Team members portfolio-wide will continue Olshan Properties’ annual ...
(Date:5/4/2016)... ... May 04, 2016 , ... ... Nurses (WOCN) Society™ and Canadian Association for Enterostomal Therapy (CAET) will be ... saving and planning tools to attendees and exhibitors for the 2016 WOCN Society ...
(Date:5/4/2016)... ... May 04, 2016 , ... ... charity program created to assist the people of their local community. The agency ... organizations and community leaders. Their hope is to bring awareness to important local ...
(Date:5/4/2016)... ... May 04, 2016 , ... Slepkow Slepkow & ... one of the top website design companies to create a state of the ... to the law firm's main practice areas. These practice areas include: real estate, ...
Breaking Medicine News(10 mins):
(Date:5/4/2016)... 4, 2016 Research ... "Global Acute lymphocytic Leukemia Market and Competitive ... offering.       (Logo: http://photos.prnewswire.com/prnh/20160330/349511LOGO ... Leukemia Market and Competitive Landscape Highlights 2016, ... pipeline products, Acute Lymphocytic Leukemia epidemiology, Acute ...
(Date:5/3/2016)... to further expand product development, strengthen its disease modeling capabilities and increase market presence. Photo - ... ... ... ... Sino-German High-Tech Fund (SGHF) is an ...
(Date:5/3/2016)... watching a film or TV show in high definition, you may not be familiar with ...  is a renowned authorized reseller of the medical industry,s top brands as well as a ... ... ... Although initially introduced ...
Breaking Medicine Technology: