Increased elastin production by progeria skin fibroblasts is controlled by the steady-state levels of elastin mRNA.
Hutchinson-Gilford progeria is a unique, rare disease with markedly accelerated aging. The average lifespan of affected individuals is 12 years. Although the biochemical basis of the syndrome is unknown, its influence appears to be primarily upon mesodermal tissues. Characteristics such as the altered appearance of the skin and the extensive and fatal involvement of the cardiovascular system led us to study elastin production in cultured skin fibroblasts from three progeroid individuals. We found tropoelastin production by progeroid cells was elevated six- to nine-fold at the protein and mRNA levels, while relative collagen synthesis was similar to control strains. There was little difference between progeroid and normal cells in expression of total protein or in total cellular mRNA content. Western blot analysis of tropoelastin from progeroid fibroblasts confirmed increased production of elastin but revealed no gross changes in the molecular mass. The significant increase in tropoelastin expression lends support to the concept that progeria results from a mesenchymal dysplasia, and offers a possible biochemical marker for the phenotype.
Sephel
G C
GC
Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee.
Sturrock
A
A
Giro
M G
MG
Davidson
J M
JM
D000293:Adolescent; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004549:Elastin / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008297:Male; D011371:Progeria / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism*; D012016:Reference Values; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D014333:Tropoelastin / Q000378:metabolism
D012333:RNA, Messenger; D014333:Tropoelastin; D004549:Elastin