Tropoelastin regulates chemokine expression in fibroblasts in Costello syndrome.
Costello syndrome is a multiple congenital anomaly associated with growth and mental retardation, cardiac and skeletal anomalies, and a predisposition to develop neoplasia. Comprehensive expression analysis revealed remarkable up-regulation of several cytokines and chemokines including Gro family proteins, interleukin-1beta (IL-1beta), IL-8 and MCP-1 but down-regulation of extracellular matrix components including collagens and proteoglycans of skin fibroblasts derived from a Japanese Costello syndrome patient characterized by significantly reduced tropoelastin mRNA, impaired elastogenesis and enhanced cell proliferation. In contrast, decreases in these chemokines and IL-1beta expression were observed in Costello fibroblastic cell lines stably expressing the bovine tropoelastin (btEln) gene and in restored elastic fibers. These results strongly suggest that the human TE gene (ELN) transfer could be applicable for the gene therapy of a group of Costello syndrome patients with reduced ELN gene expression.
Department of Medicinal Biotechnology, Institute for Medicinal Resources, Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505, Japan.
Yutaka
Y
Tatano
Reiko
R
Fujinawa
Yasunori
Y
Kozutsumi
Tsutomu
T
Takahashi
Daisuke
D
Tsuji
Naohiro
N
Takeuchi
Kohji
K
Tsuta
Goro
G
Takada
Hitoshi
H
Sakuraba
Kohji
K
Itoh
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000628:therapy; D000293:Adolescent; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D014176:Protein Biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism*; D013577:Syndrome; D014333:Tropoelastin / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation
D018925:Chemokines; D016207:Cytokines; D014333:Tropoelastin