The Therapeutic Potential for Using Relaxin to Treat Dupuyten's Contracture
John D. Lubahn, MD1; Charles Eaton, MD2; Timothy Cooney, MS1; (1)UPMC Hamot, Erie, PA, (2)Dupuytren Foundation, West Palm Beach, FL
Introduction: Current treatment options for patients with Dupuytren's contractures (DC) include steroid injections, C. histiolyticum collagenase injection, needle aponeurotomy, and excisional surgery. Recurrence rates of from 15% to 65% have been reported. The polypeptide hormone, relaxin, may provide yet another alternative. Prior studies point to downregulation of collagen and upregulation of matrix metalloproteinases, including collagenase, following relaxin dosing in fibroblasts in vitro. Reduction in smooth muscle actin content of myofibroblasts have also been observed in animal models of fibrosis. These studies provide presumptive evidence of therapeutic potential for relaxin to treat DC. The goal of this study was to determine whether the relaxin receptor, RXFP1, is expressed in biopsies of Dupuytren's nodules. Based on prior studies, we hypothesized that RXFP1 would be present, suggesting an ability of the tissue to respond to hormone therapy.
Methods: Fifty-one (51) open biopsies were screened using standard immunohistochemistry methods. Rabbit antiRXFP1 IgG was used as the primary antibody (Immundiagnostik, Bensheim, Germany). Either endometrium or myometrium was used as a positive tissue control (relaxin receptor expression). Negative controls were run with na´ve rabbit immunoglobin. Controls were run concurrent with test specimens.
Results: Tissue samples consisting of sparse, flattened cell nuclei amidst dense ECM showed little or no staining. Conversely, glands, blood vessels and areas of cell proliferation evidenced staining (Figures 1-4) Positive and negative controls stained appropriately. Overall, 30% (16/51) of the specimens stained positive for RXFP1.
Discussion: The present study suggests that most tissue representing late-stage Dupuytren's nodules do not express RXFP1 receptors. Prior studies have elucidated the role of cytokines and growth factors such as TGFB1, PDGF, EGF, and IL6 in the maintenance of the myofibroblast phenotype. Studies pertinent to hormone interaction are limited. Estrogen has been found to repress age-related fibrosis in renal interstitial cells via ER-alpha receptor. Preclinical trials using estrogen to abrogate vaginal adhesions has shown variable success in the absence of eludicating mechanism of action. The current study suggests that therapeutic potential of Dupuytren's tissue to relaxin is associated with cell proliferative activity; advanced stage disease would likely not benefit.
Significance: Current treatments for Dupuytren's disease are ineffective at disease eradication. Relaxin may offer a conservative approach to treating early stage disease.
Fig. 1: No Staining Fig.2: No Staining Fig.3: Staining (brown) Fig.4: Staining (brown)
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