Involvement of TGF-beta in skin photoaging

The goal of this thesis study was to understand the role of TGF-[beta] in skin photoaging, especially in solar elastosis. Solar elastosis, the accumulation of elastotic material in the dermal extracelluar matrix, is a major hallmark of photoaging. However, the mechanisms by which UV radiation causes solar elastosis are poorly understood. TGF-[beta] is a multifunctional cytokine involved in the regulation of extracelluar matrix and is known to be up-regulated by UVR. Involvement of reactive oxygen species (ROS) in the development of solar elastosis has been demonstrated by many studies using antioxidants and anti-inflammatory agents in the mouse skin in vivo. We hypothesized that ROS produced by TGF-[beta] are key components in the tropoelastin (TE, a soluble precursor of elastin) up-regulation in dermal fibroblasts, and that TGF-[beta] is a major regulator in the photoaging processes. Using human skin fibroblasts system in vitro, we found that ROS generated from NADPH oxidase and mitochondria are involved in the TGF-[beta] induced elastin production, and intracellular sources of ROS vary with time. We showed that both Smad and non-Smad pathways, e.g. MAPK and PKC pathways, are required for TE mRNA up-regulation by TGF-[beta].

Department dc:contributor.department

Harvard University--MIT Division of Health Sciences and Technology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2005

Author dc:creator

• Choi, Won Seon, 1975-

Advisor dc:contributor.advisor

• Irene E. Kochevar.

• Harvard University--MIT Division of Health Sciences and Technology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/33842
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/33842

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/33842