Abstract

We have recently generated a mouse strain that is deficient for the fibulin-5 gene by homologous recombination. Fibulin-5 belongs to the fibulin family of extracellular matrix proteins and is abundantly expressed in the skin, lungs, and aortas. Fibulin-5 homozygous mutant mice develop systemic elastinopathy including loose skin, emphysematous lung and tortuous and elongated aorta. Morphological studies as well as biochemical analyses revealed that fibulin-5 acts as bridging molecule between elastic fibers and the surrounding cell surface, and is essential for the final organization of elastic fibers in vivo. By utilizing fibulin-5 mutant mice, we will investigate the role of fibulin-5 in skin wound repair with respect to elastic fiber regeneration and healing. We will also explore the possibility of modulating wrinkle formation in vivo by investigating the role of fibulin-5 in physiological aging. Third, we will establish an in vitro culture system to obtain cross- linked and organized elastic fibers by establishing co-culture condition for cells over-expressing tropoelastin, fibulin-5 and cell surface integrin. These studies will provide a strong basis for a therapeutic implication for skin wound treatment and wrinkle treatment.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Center Core Grants (P30)
Project #
5P30AR041940-11
Application #
6602473
Study Section
Special Emphasis Panel (ZAR1)
Project Start
2002-06-01
Project End
2006-05-31
Budget Start
Budget End
Support Year
11
Fiscal Year
2002
Total Cost
Indirect Cost

  Institution

Name
University of Texas Sw Medical Center Dallas
Department
Type
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390

  Publications

Acharya, Asha; Baek, Seung Tae; Banfi, Serena et al. (2011) Efficient inducible Cre-mediated recombination in Tcf21 cell lineages in the heart and kidney. Genesis 49:870-7
Straud, Sarah; Zubovych, Iryna; De Brabander, Jef K et al. (2010) Inhibition of iron uptake is responsible for differential sensitivity to V-ATPase inhibitors in several cancer cell lines. PLoS One 5:e11629
Chapman, Shelby L; Sicot, F-X; Davis, Elaine C et al. (2010) Fibulin-2 and fibulin-5 cooperatively function to form the internal elastic lamina and protect from vascular injury. Arterioscler Thromb Vasc Biol 30:68-74
Yanagisawa, Hiromi; Davis, Elaine C (2010) Unraveling the mechanism of elastic fiber assembly: The roles of short fibulins. Int J Biochem Cell Biol 42:1084-93
Choi, Jiwon; Bergdahl, Andreas; Zheng, Qian et al. (2009) Analysis of dermal elastic fibers in the absence of fibulin-5 reveals potential roles for fibulin-5 in elastic fiber assembly. Matrix Biol 28:211-20
Jaeckle Santos, Lane J; Xing, Chao; Barnes, Robert B et al. (2008) Refined mapping of X-linked reticulate pigmentary disorder and sequencing of candidate genes. Hum Genet 123:469-76
Takayama, Yoshiharu; May, Petra; Anderson, Richard G W et al. (2005) Low density lipoprotein receptor-related protein 1 (LRP1) controls endocytosis and c-CBL-mediated ubiquitination of the platelet-derived growth factor receptor beta (PDGFR beta). J Biol Chem 280:18504-10
Wang, Huixia; He, Xuming; Band, Mark et al. (2005) A study of inter-lab and inter-platform agreement of DNA microarray data. BMC Genomics 6:71
Sinha, Suwan K; Zachariah, Sunny; Quinones, Herson I et al. (2002) Role of TRAF3 and -6 in the activation of the NF-kappa B and JNK pathways by X-linked ectodermal dysplasia receptor. J Biol Chem 277:44953-61
Breuer-McHam, J; Simpson, E; Dougherty, I et al. (2001) Activation of HIV in human skin by ultraviolet B radiation and its inhibition by NFkappaB blocking agents. Photochem Photobiol 74:805-10

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