Fibronectin is overproduced by keloid fibroblasts during abnormal wound healing.
Wound healing in certain individuals leads to the development of keloid tumors which exhibit abnormal collagen metabolism and an increased abundance of extracellular matrix components. Comparison of fibronectin levels in fibroblasts derived from keloids and normal dermis revealed a relative increase in intracellular and extracellular fibronectin in the keloid-derived cells. While fibronectin was similarly processed, compartmentalized, and degraded by both cell types, fibronectin biosynthesis was found to be accelerated as much as fourfold in keloid fibroblasts due to a corresponding increase in the amount of accumulated fibronectin mRNA. These changes account for the elevated steady-state level of the molecule in keloid fibroblasts and suggest that increased fibronectin in keloid lesions is due to overproduction by the wound-healing fibroblasts. Glucocorticoid treatment stimulated fibronectin biosynthesis in both normal and keloid fibroblasts. However, the amount of stimulation was less for the keloid-derived cells, indicating a limitation on maximal rates of fibronectin biosynthesis. These observations suggest that separate mechanisms act to control basal and maximal rates of fibronectin production. Biosynthesis of the 140-kilodalton fibronectin receptor was also found to be increased in keloid fibroblasts, suggesting some level of coordinate regulation for fibronectin and fibronectin receptor expression.
Babu
M
M
Department of Anatomy and Cell Biology, Tufts University Health Sciences Campus, Boston, Massachusetts 02111.
Diegelmann
R
R
Oliver
N
N
D000328:Adult; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007627:Keloid / Q000235:genetics / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000096:biosynthesis; D012867:Skin / Q000378:metabolism; D014945:Wound Healing
D005353:Fibronectins; D012333:RNA, Messenger; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic