European Journal of Molecular & Clinical Medicine

Abstract

Translational studies conducted in the Center for Cell Biology & Cancer Research at the Albany Medical College integrate the discovery of basic mechanisms underlying the development of human fibrotic disease with in vivo interventional strategies and tissue repair outcomes in animal models. This structured research program is expected to lead to the clinical adaptation of novel therapies specifically directed to the control of pathologically-relevant profibrotic genes in several organ systems. Perhaps the most mature, clinically-relevant, multidisciplinary effort focuses on molecular events underlying the pathophysiology of the renal fibrotic response to tissue injury. This program involves a network of collaborating urological surgeons, nephrologists, graduate students, pathologists, residents, transplant surgeons, basic scientists and molecular biologists and is built on a highly-collaborative framework that fosters translational interactions. This cooperative enterprise resulted in a new appreciation for the complexity of the TGF-β1-activated pathways leading to fibrotic gene expression in an in vivo model of renal injury that mimics obstructive uropathy in humans. Moreover, we have uncovered new, translationally-relevant and therapeutically-accessible, molecular targets. These are the focus of current pre-clinical studies with the goal being to assess their potential utility in the therapy of human renal fibrotic disease. Focal points: Interstitial fibrosis is a progressive disorder that frequently results in organ failure; current treatments are limited and largely ineffective. The majority of fibrotic diseases are irreversible and eventually fatal. Regardless of etiology, elevated tissue TGF-β1 levels and transcription of TGF-β1-responsive genes are linked to the activation of profibrotic signaling pathways. Plasminogen activator inhibitor-1(PAI-1) is a major causative factor in several clinically significant fibrotic syndromes. Translational research in the Center for Cell Biology & Cancer Research at Albany Medical College focuses on molecular events underlying transcriptional control of the profibrotic PAI-1 gene using an animal model of obstructive uropathy. The need for novel targeted approaches for the treatment of fibrosis highlights the clinical potential in the current probe of molecular mechanisms underlying TGF-β1-regulated PAI-1 gene control.