Research Summary:

Dr. Brosius' laboratory is developing novel models of diabetic kidney disease to understand better how this disease occurs and how to cure it. His laboratory is also testing new therapies to reduce or halt progression of diabetic kidney disease and will hopefully begin clinical trials with some of these approaches soon. His laboratory also studies how glucose transporters lead to hypertensive changes in vascular cells and how they affect vascular cell death.

Link to PubMed Citations

Selected Publications:

Siu BB, Saha J, Smoyer WE, Sullivan KA, Brosius FC III. Reduction in podocyte density as a pathologic feature in early diabetic nephropathy in rodents: prevention of by lipoic acid treatment, BMC Nephrology 2006, 7:6 ( 15 Mar 2006 )

Zhou, J., Deo, B., Hosoya, K., Terasaki, T., Brosius, F.C., Obrosova, I. , and Kumagai, A.K. Increased JNK Phosphorylation and oxidative stress in response to increased glucose flux through increased GLUT1 expression in rat retinal endothelial cells. Invest Ophthalmol Vis Sci. 2005;46:3403-10.

Park JL, Loberg RD, Duquaine D, Zhang H, Deo BK, Ardanaz N, Coyle J, Atkins KB, Schin M, Charron MJ, Kumagai AK, Pagano PJ, Brosius FC III. . The GLUT4 facilitative glucose transporter specifically and differentially contributes to agonist-induced vascular reactivity in mouse aorta. Arteriosclerosis, Thrombosis, and Vascular Biology, 2005;25: 1596-1602.

Breyer MD, Bottinger E, Brosius FC, Coffman TM, Fogo A, Harris RC, Heilig CW, Sharma K. Diabetic nephropathy: Of mice and men. Adv Chronic Kidney Dis. 2005;12:128-45.

Brosius FC III, Heilig CW. Glucose transporters in diabetic nephropathy. Pediatr Nephrol. 2005;20:447-51.

Breyer MD, Bottinger E, Brosius FC 3rd, Coffman TM, Harris RC, Heilig CW, Sharma K. Mouse Models of Diabetic Nephropathy. J Am Soc Nephrol. 2005; 16:27 -45

Atkins KB, Northcott C, Watts S, Brosius FC III. Effect of PPARγ ligands on hypertension and vascular smooth muscle marker expression, Am J Physiol. 2005 Jan;288:H235-H243.

Vega-Warner V, Ransom RF, Brosius FC, Smoyer WE. Induction of Podocyte Antioxidant Enzymes Precedes Injury by Puromycin Aminonucleoside In Vitro, Kidney International, 2004;66:1881-9.

Shen H, Smith DE , Keep RF, Brosius FC III. Immunolocalization of the proton-coupled oligopeptide transporter PEPT2 in rat brain. Mol Pharm 2004;1:248-256.

Park JL, Heilig CW, Brosius FC III. GLUT1-Deficient Mice Exhibit Impaired Endothelium-Dependent Vascular Relaxation, Eur J Pharmacol. 2004;496:213-4.

Slovut DP, Mehta SH, Dorrance AM, Brosius FC, Watts SW, Webb RC. Increased vascular sensitivity and connexin 43 expression after sympathetic denervation. Cardiovas Res, 2004, 62:388-96.

Heilig CW, Saunders T, Brosius FC III, Moley K, Heilig K, Baggs R, Guo L, Conner D. Glucose transporter-1-deficient mice exhibit impaired development and deformities that are similar to diabetic embryopathy. Proc Natl Acad Sci U S A. 2003;100:15613-8.

Heilig C, Brosius F, Siu B, Concepcion L, Mortensen R, Heilig K, Zhu M, Weldon R, Wu G, Conner D. Implications of GLUT1-Haplodeficiency in Embryonic Stem Cells for their Survival in Response to Hypoxic Stress, Am J Pathol, 2003;163:1873-85.

Brosius FC III. How glucose and glucose transporters protect cardiac myocytes. J Mol Cell Cardiol 2003; 35:1187-1189.

Loberg RD , Northcott CA , Watts SW, Brosius FC III. Role of GSK-3 activity in arterial reactivity during DOCA-salt hypertension. Hypertension 2003;41:898-902.

Shen H, Smith DE,. Keep RF, Xiang J, Brosius FC III. Targeted Disruption of the PEPT2 Gene Markedly Reduces Dipeptide Uptake in Choroid Plexus, J Biol Chem 2003;278:4786-91.

Weigert C, Brodbeck K, Brosius FC III, Huber M, Lehmann R, Friess U, Aulwurm S, Häring H, Schleicher ED, Heilig CW. Evidence for a novel TGF-β1-independent mechanism of fibrosis in mesangial cells overexpressing glucose transporters, Diabetes. 2003;52:527-35.

Loberg RD, Vesely E, Brosius FC III. Enhanced glycogen synthase kinase-3β activity mediates hypoxia-induced apoptosis of vascular smooth muscle cells and is prevented by glucose transport and metabolism, J Biol Chem 2002; 277:41667-41673.

Malhotra R, Tyson D, Kumagi AK , Brosius FC III. Glucose uptake and adenoviral mediated GLUT-1 infection HIF-1α levels and decreases hypoxia-induced apoptosis in cardiac myocytes, J Mol Cell Cardiol 2002; 34:1063-1073.

Banes AKL, Loberg RD, Brosius FC III, Watts SW. Inability of Serotonin to Activate the c-Jun N-terminal Kinase and p38 Kinase Pathways in Rat Aortic Vascular Smooth Muscle Cells, BMC Pharmacology 2001, 1:8.

Malhotra R, Lin Z, Vincenz C, Brosius FC III. Hypoxia-induced apoptosis in Jurkat cells progresses through two independent pathways differentially regulated by glucose uptake, Am J Physiol (Cell), 2001; 281:C1596-1603.

Atkins, KB, Johns D, Watts S, Webb RC, Brosius FC III. Decreased vascular glucose transporter expression and glucose uptake in DOCA-salt hypertension, J Hypertens 2001; 19:1581-1587.

Shen H, Smith DE, Brosius FC III. Developmental expression of PEPT1 and PEPT2 in rat small intestine and kidney, Pediatr Res, 2001; 49:789-795.

Malhotra JD, Chen C, Abriel H, Malhotra R, Mattei LN, Brosius FC, Kass RS, Isom LL. Characterization of sodium channel α and β subunits in cardiac myocytes, Circulation, 2001;103:1303-10.

Heilig CW, Kreisberg JI, Freytag S, Murakami T, Ebina Y, Guo L, Heilig K, Jin Y, Loberg R, Henry D, Brosius FC III. Antisense-GLUT1 protects mesangial cells from D-glucose-induced transporter and fibronectin expression, Am J Physiol, 2001; 280:F657-666.

Lin Z, Weinberg JM, , Merritt S, Holzman LB, Brosius FC III. Increased GLUT1 expression prevents hypoxia-induced apoptosis and cJun-NH2-terminal kinase activation in vascular smooth muscle cells, Am J Physiol 2000; 278: E958-E966.