Navigation Links
Penn Dental Medicine team identifies molecule critical to healing wounds
Date:11/15/2013

Skin provides a first line of defense against viruses, bacteria and parasites that might otherwise make people ill. When an injury breaks that barrier, a systematic chain of molecular signaling launches to close the wound and re-establish the skin's layer of protection.

A study led by researchers from the University of Pennsylvania's School of Dental Medicine now offers a clearer explanation of the role of one of the players in the wound-healing process, a molecule called FOX01. Contrary to what had been expected, FOX01 is critical to wound healing, providing researchers with a possible new target for drugs that could help speed that process for people with impaired wound healing.

Senior author Dana Graves is a professor in Penn Dental Medicine's Department of Periodontics and is vice dean for scholarship and research. He collaborated on the study with Penn's Bhaskar Ponugoti, Fanxing Xu, Chenying Zhang, Chen Tian and Sandra Pacio.

A critical element of wound healing involves the movement of keratinocytes, the primary cells comprising the epidermis, or the outer layer of skin. Previous research had found that FOX01 was expressed at higher levels in wounds, but scientists did not understand what role the molecule was playing. In other scenarios, such as in cancer cells, FOX01 promotes cell death and interferes with the cell reproduction, two actions that would seem to be detrimental to healing,

To investigate the role of FOX01 in wound healing, Graves and colleagues bred mice that lacked the protein in their keratinocytes and then observed the wound healing process in these mice compared to mice with normal FOX01.

"We thought that deleting FOX01 would speed up the wound-healing process," Graves said, "but in fact it had the opposite effect."

The mice that lacked FOX01 showed significant delays in healing. Whereas all wounds on control mice were healed after one week, all of the experimental mice still had open wounds.

Digging deeper into this counterintuitive finding, the researchers examined the effect of reducing FOX01 levels on other genes known to play a role in cell migration. They found that many of these genes were significantly reduced, notably TGF-β1, a critical growth factor in wound repair. When the team added TGF-β1 to cells lacking FOX01, the cells behaved normally and produced the proper suite of molecules needed for healing, indicating that FOX01 acts upstream of TGF-β1 in the signaling pathway triggered during the healing process.

Further experimenting revealed that mice lacking FOX01 had evidence of increased oxidative stress, which is detrimental to wound healing.

"The wound healing environment is a stressful environment for the cell," Graves said. "It appears that upregulation of FOX01 helps protect the cell against oxidative stress."

The fact that FOX01 behaves in this unexpected way could have to do with the specialized microenvironment of a cell in a wound, Graves noted. While FOX01 does indeed promote cell death when it is highly activated, it does the opposite when moderately activated. Which activity it promotes depends on the environment in which it is acting.

Taken together, the study's findings demonstrate that FOX01 plays an integral role in two key processes in wound healing: activation of TGF-β1 and protecting the cell against oxidative damage. Its involvement in these aspects of healing make it a potential target for pharmaceuticals that could help speed healing.

"If you had a small molecule that increased FOX01 expression, you might be able to upregulate TGF-β1 as well as protect against the oxidative stress associated with wound healing," Graves said.


'/>"/>

Contact: Katherine Unger Baillie
kbaillie@upenn.edu
215-898-9194
University of Pennsylvania
Source:Eurekalert  

Related biology news :

1. Dental X-rays linked to common brain tumor
2. 2 Cell Transplantation studies impact dental stem cell research for therapeutic purposes
3. Measuring mercury: Common test may overestimate exposure from dental amalgam fillings
4. ACMG releases report on incidental findings in clinical exome and genome sequencing
5. Accidental discovery may lead to improved polymers
6. Surge in children accidentally eating marijuana-laced foods
7. CWRU dental researchers NIDCR grant targets oral bacteria and fetal death link
8. Flow restrictors may reduce young childrens accidental ingestion of liquid medications
9. NYU School of Medicine presents 2012 Dart/NYU Biotechnology Achievement Awards
10. Advances in personalized medicine for lung cancer
11. Not by DNA alone: How the epigenetics revolution is fostering new medicines
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Penn Dental Medicine team identifies molecule critical to healing wounds
(Date:2/10/2017)... 10, 2017 Research and Markets ... "Personalized Medicine - Scientific and Commercial Aspects" to their ... ... is integrated with therapy for selection of treatment as well ... and prevention of disease in modern medicine. Biochip/microarray technologies and ...
(Date:2/8/2017)... 2017  Aware, Inc. (NASDAQ: AWRE ), a ... results for its quarter and year ended December 31, 2016. ... was $3.9 million compared to $6.9 million in the same ... 2016 was $0.6 million compared to $2.6 million in the ... of 2016 was $0.5 million, or $0.02 per diluted share, ...
(Date:2/8/2017)... Feb. 7, 2017 Report Highlights ... 2021 from $8.3 billion in 2016 at a compound ... 2021. Report Includes - An overview of the ... trends, with data from 2015 and 2016, and projections ... Segmentation of the market on the basis of product ...
Breaking Biology News(10 mins):
(Date:2/16/2017)... WEST PALM BEACH, Fla. , Feb. 16, ... molecular diagnostics company revolutionizing the development of liquid ... that it has entered into an exclusive license ... who will distribute MDNA,s proprietary liquid biopsy test ... in South Korea . This ...
(Date:2/16/2017)... 16, 2017   Biostage, Inc. (Nasdaq: ... company developing bioengineered organ implants to treat cancers and ... announced today the closing on February 15, 2017 of ... common stock and warrants to purchase 20,000,000 shares of ... The offering was priced at $0.40 per share of ...
(Date:2/16/2017)... , Feb. 16, 2017  Champions Oncology, Inc. ... the development and sale of advanced technology solutions and ... drugs, today announced the addition of new cohorts of ... These new models will expand Champions, product line in ... and neck cancer, AML, and non-small cell lung cancer ...
(Date:2/16/2017)... and NEW YORK , Feb. 16, ... completion of their $7M Series B financing, adding an ... the $3.5M led by Mesa Verde Venture Partners and ... resources will be directed towards further accelerating commercial adoption ... comprehensive genomic profiling test and expanding the Paradigm cancer ...
Breaking Biology Technology: