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Agnes B. Fogo, M.D.

Professor
Pathology

Professor
Medicine

Research keywords

Chronic kidney disease, PAI-1, renin angiotensin system

Research description

Our group focuses on mechanisms of progression of chronic kidney disease (CKD), including the possibility of remodeling and regression of existing sclerosis. We have a long standing interest in the renin angiotensin aldosterone system (RAAS). Our work has also focused on the interaction of the RAAS with plasminogen activator inhibitor-1 (PAI-1). Angiotensin directly induces PAI-1 both in vitro and in vivo, with augmentation of this induction by aldosterone. Beyond its effects on blood pressure, inhibitors of the RAAS thus have effects on PAI-1, which not only modifies fibrinolysis, but also proteolysis. Thus, increased PAI-1 is associated with increased sclerosis. Our research has focused on these interactions, investigating mechanisms of amelioration of progression and possible regression of existing glomerulosclerosis. In addition to non-hemodynamic actions of the RAAS, which imply that greater than usual antihypertensive doses could have greater benefit, we also study mechanisms of capillary growth and remodeling, using both in vivo confocal analysis and genetic manipulation of the podocytes, and parallel in vitro studies of endothelial cells and podocytes.
A second important component of progressive kidney disease is the tubulointerstitial fibrosis that is a constant in CKD. We have investigated mechanisms of interaction of parenchymal cells and infiltrating cells, in particular monocyte-macrophages. Our studies also investigate possible contribution of epithelial-mesenchymal transition (EMT), whereby injured tubular epithelial cells may become more fibroblast-like and enter the interstitium, contributing to collagen accumulation and thus fibrosis. Creating bone marrow chimeric mice allows separate genetic manipulation of the parenchymal elements and the bone marrow-derived elements in investigating interactions of these cells and the effects on progressive fibrosis. Use of various knock-out animals, including those of the plasmin/plasminogen activator system and of the TGF-beta activator, beta6 integrin, has allowed the dissection of mechanisms related to the RAAS and interaction with PAI-1 and TGF-beta. We have also by proteomic studies identified thymosin beta4 as a potential modulator of fibrosis, and currently study its interaction with the RAS.
6 integrin, has allowed the dissection of mechanisms related to the RAAS and interaction with PAI-1 and TGF-β.

Last updated on 2010-11-02

Zhang, M.

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