The Imbalanced Expression of Matrix Metalloproteinases in Nephrogenic Systemic Fibrosis PDF Print E-mail
Monday, 16 August 2010 10:23
Brent C. Kelly, MD, Leslie Scroggins Markle, MD, Jennifer L. Vickers, MD, Matthew S. Petitt, DO, Sharon S. Raimer, MD, and Catherine McNeese, MD

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-b 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 a-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 a-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 a-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. ( J Am Acad Dermatol 2010;63:483-9.)

Login to download your own copy of the full and original article from the link provided below

 
More articles :

» 1st Systemic Sclerosis World Congress

The world's very first Systemic Sclerosis World Congress is to be held in Florence, Italy, next week from February 11-13th 2010. Carded primarily as an interdisciplinary conference for cardiologists, dermatologists, nephrologists, pulmonologists and...

» Scleroderma and Pregnancy

In an ideal world, men and women would be able to start their families with no difficulties or problems.  However, there are many issues that can complicate matters and Scleroderma and Pregnancy is one of those issues. It is very important to...

» 7 Tips For Balancing Rest and Activity

I wanted to help patients and my friends by sharing some helpful tips about Scleroderma, an autoimmune disease in which the body attacks itself by destroying its own cells and functions. The effects of are quite severe and can affect a patient’s...

» New Study Will Explore Impact of Exercise on Pulmonary Hypertension

For sufferers of Pulmonary Arterial Hypertension (PAH), maintaining healthy heart function isn't as simple as going for a jog every morning. Patients need to do all they can to slow damage to their heart, and exercise can improve potentially improve...

» Blocking TGFβ via Inhibition of the αvβ6 Integrin: A Possible Therapy for Systemic Sclerosis Interstitial Lung Disease

Tamiko R. Katsumoto, Shelia M. Violette, and Dean SheppardReceived 27 May 2011; Accepted 15 August 2011Interstitial lung disease (ILD) is a commonly encountered complication of systemic sclerosis (SSc) and accounts for a significant proportion of...

» Jefferson Researchers Identify Mechanism Behind Fibrotic Disorder

Scientists from the of Thomas Jefferson University are now several steps closer to understanding the mechanism behind a novel systemic fibrotic disorder that affects some patients with renal insufficiency who receive imaging contrast agents for...

Add comment

Do feel free to leave your comments, as they would add value and knowledge to the community. However, please refrain from making any disparaging, uninformed, or unrelated comments. Thanks :)

Security code
Refresh