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Utpal Sen, Ph.D.

by cdhugh01 — last modified Nov 10, 2008 10:08 AM

USen
u0sen001@louisville.edu
Assistant Professor
University of Kalyani, India, 2001 



Renal disease, Renovascular remodeling and Hypertension

The goal of my research endeavor is to understand the mechanism of glomerular remodeling process during various disease stages, such as cardiovascular disease, hypertension and diabetes. These pathophysiological conditions drives glomerular vascular damage through reactive oxygen species (ROS)-induced endothelial injury, inflammation, disrupting matrix metalloproteinases (MMPs) / tissue inhibitor of matrix metalloproteinases (TIMPs) balance, and increased matrix formation. The increased matrix protein, such as collagen leads to glomerulosclerosis and impaired renal function. The kidney, in addition to its normal physiological functions, also plays a major role in homocysteine, a non-protein amino acid clearance, and plasma total homocysteine increases as renal function declines. At physiological pH homocysteine can undergo oxidation and produces a variety of ROS. This further exacerbates the cardiovascular disease complication. Two enzymes, cystathionine-b-synthase and cystathionine-g-lyase clear homocysteine from the body to produce hydrogen sulfide (H2S). My laboratory have recently shown that high level of homocysteine down regulates cystathionine-g-lyase, resulting decrease in the generation of the novel endogenous third gaseous substance, H2S. Because H2S is a strong antioxidant and increases the anti-oxidative properties of other physiological antioxidants, we hypothesize that amelioration of endogenous H2S can modulate homocysteine-induced renal failure. Currently we are pursuing research to test our hypothesis using both in vivo animal model and in vitro cell culture.  

Recent Publications:

  1. Sen U, Vacek TP, Hughes WM, Kumar M, Moshal KS, Tyagi N, Metreveli N, Hayden MR, Tyagi SC. Cardioprotective role of sodium thiosulfate on chronic heart failure by modulating endogenous H2S generation. Pharmacology 82: 201-213, 2008.
  2. Sen U, Rodriguez WE, Tyagi N, Kumar M, Kundu S, Tyagi SC. Ciglitazone, a PPARg agonist ameliorates diabetic nephropathy in part through homocysteine clearance. Am J Physiol Endocrinol Metab 2008 Sep 9. [Epub ahead of print] PMID: 18780770 [PubMed - as supplied by publisher].
  3. Rodriguez WE, Sen U, Tyagi N, Kumar M, Carneal G, Aggrawal D, Newsome J, Tyagi SC. PPAR gamma agonist normalizes glomerular filtration rate, tissue levels of homocysteine, and attenuates endothelial-myocyte uncoupling in alloxan induced diabetic mice. Int J Biol Sci 4: 236-244, 2008.
  4. Sen U, Herrmann M, Herrmann W, Tyagi SC. Synergism between AT1 receptor and hyperhomocysteinemia during vascular remodeling. Clin Chem Lab Med 45: 1771-1776, 2007.
  5. Sen U, Tyagi N, Kumar M, Moshal KS, Rodriguez WE, Tyagi SC. Cystathionine-beta-synthase gene transfer and 3-deazaadenosine ameliorate inflammatory response in endothelial cells. Am J Physiol Cell Physiol 293: C1779-C1787, 2007.  
  6. Sen U, Moshal KS, Singh M, Tyagi N, Tyagi SC. Homocysteine-induced biochemical stress predisposes to cytoskeletal remodeling in stretched endothelial cells. Mol Cell Biochem 302: 133-143, 2007.
  7. Sen U, Tyagi N, Moshal KS, Kartha GK, Rosenberger D, Henderson BC, Joshua IG, Tyagi SC. Cardiac synchronous and dys-synchronous remodeling in diabetes mellitus. Antioxid Redox Signal  9: 971-978, 2007.
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