The hyperthermia-enhanced association between tropoelastin and its 67-kDa chaperone results in better deposition of elastic fibers.
The results of our in vitro experiments indicate that exposing cultured human aortic smooth muscle cells and dermal fibroblasts to 39 to 41 °C induces a significant up-regulation in the net deposition of elastic fibers, but not of collagen I or fibronectin, and also decreases the deposition of chondroitin sulfate-containing moieties. We further demonstrate that mild hyperthermia also rectifies the insufficient elastogenesis notable in cultures of fibroblasts derived from the stretch-marked skin of adult patients and in cultures of dermal fibroblasts from children with Costello syndrome, which is characterized by the accumulation of chondroitin 6-sulfate glycosaminoglycans that induce shedding and inactivation of the 67-kDa elastin-binding protein. We have previously established that this protein serves as a reusable chaperone for tropoelastin and that its recycling is essential for the normal deposition of elastic fibers. We now report that hyperthermia not only inhibits deposition of chondroitin 6-sulfate moieties and the consequent preservation of elastin-binding protein molecules but also induces their faster recycling. This, in turn, triggers a more efficient preservation of tropoelastin, enhancement of its secretion and extracellular assembly into elastic fibers. The presented results encourage using mild hyperthermia to restore elastic fiber production in damaged adult skin and to enhance elastogenesis in children with genetic elastinopathies.
Murphy
Brooke A
BA
Cardiovascular Research Program, The Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 1X8, Canada.
Bunda
Severa
S
Mitts
Thomas
T
Hinek
Aleksander
A
D000328:Adult; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D056685:Costello Syndrome / Q000378:metabolism* / Q000473:pathology; D004547:Elastic Tissue / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006025:Glycosaminoglycans; D018869:Heat-Shock Response; D006801:Humans; D007223:Infant; D008297:Male; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014333:Tropoelastin / Q000378:metabolism*
D006025:Glycosaminoglycans; D011956:Receptors, Cell Surface; D014333:Tropoelastin; C054901:elastin-binding proteins