Nephrogenic systemic fibrosis: evidence for oxidative stress and bone marrow-derived fibrocytes in skin, liver, and heart lesions using a 5/6 nephrectomy rodent model
| Autor: | Brent, Wagner, Chunyan, Tan, Jeffrey L, Barnes, Seema, Ahuja, Thomas L, Davis, Yves, Gorin, Fabio, Jimenez |
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| Rok vydání: | 2011 |
| Předmět: |
Antigens
Differentiation Myelomonocytic Contrast Media Antigens CD34 Nephrectomy Collagen Type I Nephrogenic Fibrosing Dermopathy Antigens CD Bone Marrow Animals Humans Skin Myocardium Dermis Organ Size Fibroblasts Fibrosis Magnetic Resonance Imaging Rats Inbred F344 Extracellular Matrix Rats Disease Models Animal Oxidative Stress Skinfold Thickness Liver Female Factor XIIIa Reactive Oxygen Species |
| Zdroj: | The American journal of pathology. 181(6) |
| ISSN: | 1525-2191 |
| Popis: | Nephrogenic systemic fibrosis (NSF) is associated with gadolinium-based magnetic resonance imaging (MRI) contrast exposure in the setting of acute or chronic renal compromise. It has been proposed that circulating fibrocytes mediate the disease. A study was conducted to determine whether bone marrow-derived fibroblast precursors are involved in contributing to organ fibrosis in MRI contrast-treated rodents with renal insufficiency. Rats status post 5/6 nephrectomy underwent bone marrow transplant from human placental alkaline phosphatase (hPAP)-expressing donors. After engraftment, animals were treated with gadolinium-based MRI contrast (2.5 mmol/kg IP), during weekdays for 4 weeks, or an equivalent volume of normal saline. Dermal cellularity in the contrast-treated group was fourfold that of control. Skin cells from the contrast-treated group demonstrated greater hPAP expression with co-expression of pro-collagen I and α-smooth muscle actin-positive stress fibers. Donor and host cells expressed CD34. Dihydroethidium staining of skin was greater in the contrast-treated animals, indicating oxidative stress. This was abrogated when the animals were co-administered the superoxide dismutase mimetic tempol. In conclusion, a bone marrow-derived cell population is increased in the dermis of MRI contrast-treated rodents. The cell markers are consistent with fibrocytes mediating the disease. These changes correlate with oxidative stress and expression of Nox4, suggestive of a novel therapeutic target. Elucidation of the mechanisms of MRI contrast-induced fibrosis may aid in discovering therapies to this devastating disease. |
| Databáze: | OpenAIRE |
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