Transglutaminases: the missing link in nephrogenic systemic fibrosis.
Nephrogenic systemic fibrosis (NSF), also known as nephrogenic fibrosing dermopathy (NFD), occurs in renal failure patients after gadolinium contrast exposure. The fibrosis of the dermis and subcutaneous septae accompanies fibrosis of other organs, including the heart, liver, lungs, and muscle. The fibrotic skin demonstrates increased dermal collagen, fibroblasts, and mucin. The mechanism by which gadolinium is associated with fibrosis is not known. We tested the hypothesis that upregulation of transglutaminases contributes to the fibrosis seen in the organs, including skin, of renal failure patients exposed to gadolinium contrast. We performed immunohistochemical studies using antibodies to transglutaminase-2, factor XIIIa, transglutaminase isopeptide, and the histiocyte marker CD68 on five archived skin biopsies of NSF. The results indicate that the dermal fibroblasts and histiocytes of NSF express transglutaminase-2, CD68, factor XIIIa, and transglutaminase isopeptide, indicating increased expression and/or activation of transglutaminases in NSF. We recommend further research into the use of transglutaminase inhibitors in the treatment and prevention of NSF.
Parsons
Amy C
AC
Department of Pathology, Wake Forest University Baptist Medical Center, Winston Salem, NC 27157-1045, USA.
Yosipovitch
Gil
G
Sheehan
Daniel J
DJ
Sangüeza
Omar P
OP
Greenberg
Charles S
CS
Sane
David C
DC
D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D003287:Contrast Media / Q000009:adverse effects; D026122:Factor XIIIa / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology; D005355:Fibrosis / Q000139:chemically induced; D005682:Gadolinium / Q000009:adverse effects; D006644:Histiocytes / Q000201:enzymology / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000201:enzymology*; D012867:Skin / Q000201:enzymology* / Q000473:pathology*; D012871:Skin Diseases / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D013577:Syndrome; D011503:Transglutaminases / Q000378:metabolism*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003287:Contrast Media; D026122:Factor XIIIa; D005682:Gadolinium; D011503:Transglutaminases; C067980:CD68 antigen, human; D000097382:CD68 Molecule