TY - JOUR
T1 - The imbalanced expression of matrix metalloproteinases in nephrogenic systemic fibrosis
AU - Kelly, Brent C.
AU - Markle, Leslie Scroggins
AU - Vickers, Jennifer L.
AU - Petitt, Matthew S.
AU - Raimer, Sharon S.
AU - McNeese, Catherine
N1 - Funding Information:
Financial support from the Department of Dermatology, University of Texas Medical Branch .
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/9
Y1 - 2010/9
N2 - Background: Nephrogenic systemic fibrosis (NSF) occurs in patients with renal dysfunction and gadolinium exposure. Although little is known about the pathogenesis of this disease, increased expression of transforming growth factor-β has been recently demonstrated. Other fibrosing conditions have been shown to express an imbalance in matrix metalloproteinase (MMP) expression and their corresponding inhibitors. Myofibroblast differentiation, in which cells often express α-smooth muscle actin and achieve the ability to contract, is also a hallmark of fibrosis. Objective: We theorized that NSF may overexpress tissue inhibitor of metalloproteinase-1 (TIMP-1), while simultaneously showing decreased expression of MMP-1. As a secondary aim, we sought to evaluate the presence of smooth muscle actin in our samples. Methods: We applied immunohistochemistry to 16 skin biopsies from 10 patients with NSF using antibodies to TIMP-1, MMP-1, MMP-2, MMP-9, and α-smooth muscle actin. Samples from normal skin, scar, keloid and scleroderma were stained for comparison. Results: TIMP-1 was strongly expressed in all NSF specimens compared to normal skin. MMP-1 expression was nearly absent in all tested samples. In all 16 NSF cases, the dermal spindle cells did not stain for α-smooth muscle actin. MMP-2 and MMP-9 expression was variable but was increased compared to normal skin. Limitations: The expression is semiquantitative and based on immunohistochemistry and unconfirmed by other techniques. Conclusions: In NSF, TIMP-1 is strongly expressed and MMP-1 is nearly absent, characteristic of the MMP imbalances seen in other fibrosing processes. Using smooth muscle actin immunohistochemistry, there was no evidence of myofibroblast differentiation.
AB - Background: Nephrogenic systemic fibrosis (NSF) occurs in patients with renal dysfunction and gadolinium exposure. Although little is known about the pathogenesis of this disease, increased expression of transforming growth factor-β has been recently demonstrated. Other fibrosing conditions have been shown to express an imbalance in matrix metalloproteinase (MMP) expression and their corresponding inhibitors. Myofibroblast differentiation, in which cells often express α-smooth muscle actin and achieve the ability to contract, is also a hallmark of fibrosis. Objective: We theorized that NSF may overexpress tissue inhibitor of metalloproteinase-1 (TIMP-1), while simultaneously showing decreased expression of MMP-1. As a secondary aim, we sought to evaluate the presence of smooth muscle actin in our samples. Methods: We applied immunohistochemistry to 16 skin biopsies from 10 patients with NSF using antibodies to TIMP-1, MMP-1, MMP-2, MMP-9, and α-smooth muscle actin. Samples from normal skin, scar, keloid and scleroderma were stained for comparison. Results: TIMP-1 was strongly expressed in all NSF specimens compared to normal skin. MMP-1 expression was nearly absent in all tested samples. In all 16 NSF cases, the dermal spindle cells did not stain for α-smooth muscle actin. MMP-2 and MMP-9 expression was variable but was increased compared to normal skin. Limitations: The expression is semiquantitative and based on immunohistochemistry and unconfirmed by other techniques. Conclusions: In NSF, TIMP-1 is strongly expressed and MMP-1 is nearly absent, characteristic of the MMP imbalances seen in other fibrosing processes. Using smooth muscle actin immunohistochemistry, there was no evidence of myofibroblast differentiation.
KW - Matrix metalloproteinase
KW - Myofibroblast
KW - Nephrogenic fibrosing dermopathy
KW - Nephrogenic systemic fibrosis
KW - Smooth muscle actin
KW - Tissue inhibitor of matrix metalloproteinase
KW - Transforming growth factor
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U2 - 10.1016/j.jaad.2009.09.006
DO - 10.1016/j.jaad.2009.09.006
M3 - Article
C2 - 20708474
AN - SCOPUS:77955864516
SN - 0190-9622
VL - 63
SP - 483
EP - 489
JO - Journal of the American Academy of Dermatology
JF - Journal of the American Academy of Dermatology
IS - 3
ER -