Utpal Sen, Ph.D., F.A.H.A.

 

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


Renal vascular pathophysiology in hypertension and diabetes

The overall goal of our laboratory is to delineate the mechanisms of kidney injury and dysfunction in hypertension and diabetes. These pathophysiological conditions, in conjunction with epigenetic influences, such as aberrant DNA methylation, non-coding RNAs, and dysbiosis in gut microbiota, drive glomerular-tubulointerstitial damage, and increase matrix formation leading to glomerular-tubulointerstitial fibrosis and impairs renal function.

Kidney, in addition to its normal physiological function, also plays a major role in hydrogen sulfide (H2S) biosynthesis. Emerging evidence indicates that H2S is an important gaseous molecule with numerous physiological effects. In hypertension and diabetes, pathophysiological kidney remodeling leads to diminished H2S biosynthesis, which further reduces the renal outcome. We have focused our research on delineating whether an increase of H2S to the physiological level, either by drug delivery or epigenetic modulation, has any protective role in adverse renovascular remodeling and dysfunction during hypertension and diabetes.

Recent publications: selected from more than 70 articles

Research articles

  1. Majumder S, Ren L, Pushpakumar S, Sen U. Hydrogen sulphide mitigates homocysteine-induced apoptosis and matrix remodelling in mesangial cells through Akt/FOXO1 signalling cascade Cellular Signalling. Cell Signal. 2019; 61:66-77. PMID: 31085234.
  2. Papu John AS, Kundu S, Pushpakumar S, Amin M, Tyagi SC, Sen U. Hydrogen sulfide inhibits Ca2+-induced mitochondrial permeability transition pore (MPTP) opening in type-1 diabetes. Am J Physiol - Endocrinol Metab. 2019; 317(2):E269-E283. PMID: 31039005.
  3. Pushpakumar S, Kundu S, Sen U. Hydrogen Sulfide Protects Hyperhomocysteinemia-Induced Renal Damage by Modulation of Caveolin and eNOS Interaction. Sci. Rep. 2019; 9(1):2223. PMID: 30778103.
  4. Weber GJ, Purkayastha B, Ren L, Pushpakumar S, Sen U. Hypertension exaggerates renovascular resistance via miR-122 associated stress-response in aging. J. Hypertension. 2018; 36(11):2226-2236. PMID: 30256768.
  5. Weber GJ, Foster J, Pushpakumar SB, Sen U. Altered microRNA regulation of short chain fatty acid receptors in the hypertensive kidney is normalized with hydrogen sulfide supplementation. Pharmacol Res. 2018; 134:157-165. PMID: 29909116.
  6. John AMSP, Kundu S, Pushpakumar S, Fordham M, Weber G, Mukhopadhyay M, Sen U. GYY4137, a Hydrogen Sulfide Donor Modulates miR194-Dependent Collagen Realignment in Diabetic Kidney. Sci Rep. 2017; 7(1):10924. PMID: 28883608.
  7. Pushpakumar S, Ren L, Kundu S, Gamon A, Tyagi SC, Sen U. Toll-like Receptor 4 Deficiency Reduces Oxidative Stress and Macrophage Mediated Inflammation in Hypertensive Kidney. Sci Rep. 2017; 7(1):6349. PMID: 28743964.
  8. Weber GJ, Pushpakumar SB, Sen U. Hydrogen sulfide alleviates hypertensive kidney dysfunction through an epigenetic mechanism. Am J Physiol Heart Circ Physiol. 2017; 312(5):H874-H885. PMID: 28213404.
  9. Pushpakumar S, Kundu S, Narayanan N, Sen U. DNA hypermethylation in hyperhomocysteinemia contributes to abnormal extracellular matrix metabolism in the kidney. FASEB J. 2015; 29(11):4713-25. PMID: 26224753.
  10. Kundu S, Pushpakumar S, Sen U. MMP-9- and NMDA receptor-mediated mechanism of diabetic renovascular remodeling and kidney dysfunction: hydrogen sulfide is a key modulator. Nitric Oxide. 2015; 46:172-85. PMID: 25659756.
  11. Kundu S, Pushpakumar S, Khundmiri SJ, Sen U. Hydrogen sulfide mitigates hyperglycemic remodeling via liver kinase B1-adenosine monophosphate-activated protein kinase signaling. Biochim Biophys Acta. 2014; 1843(12):2816-26. PMID: 25127936.
  12. Pushpakumar SB, Kundu S, Metreveli N, Sen U. Folic Acid Mitigates Angiotensin-II-Induced Blood Pressure and Renal Remodeling. PLoS One. 2013; 8(12):e83813. PMID: 24386282.
  13. Pushpakumar SB, Kundu S, Metreveli N, Tyagi SC, Sen U. Matrix Metalloproteinase Inhibition Mitigates Renovascular Remodeling in Salt-Sensitive Hypertension. Physiol Rep. 2013;1(3):e00063. PMID: 24159376.
  14. Pushpakumar S, Kundu S, Pryor T, Givvimani S, Lederer E, Tyagi SC, Sen U. Angiotensin-II induced hypertension and renovascular remodelling in tissue inhibitor of metalloproteinase 2 knockout mice. J Hypertens. 2013; 31(11):2270-81; discussion 2281. PMID: 24077247.
  15. Kundu S, Pushpakumar SB, Tyagi A, Coley D, Sen U. Hydrogen sulfide deficiency and diabetic renal remodeling: role of matrix metalloproteinase-9. Am J Physiol Endocrinol Metab. 2013; 304(12):E1365-78. PMID: 23632630.
  16. Sen U, Sathnur PB, Kundu S, Givvimani S, Coley DM, Mishra PK, Qipshidze N, Tyagi N, Metreveli N, Tyagi SC. Increased endogenous H2S generation by CBS, CSE, and 3MST gene therapy improves ex vivo renovascular relaxation in hyperhomocysteinemia. Am J Physiol Cell Physiol. 2012; 303(1):C41-51. PMID: 22517358.
  17. Givvimani S, Munjal C, Tyagi N, Sen U, Metreveli N, Tyagi SC. Mitochondrial division/mitophagy inhibitor (Mdivi) ameliorates pressure overload induced heart failure. PLoS One. 2012; 7(3):e32388. PMID: 22479323.
  18. Basu P, Qipshidze N, Tyagi SC, Sen U. Remodeling in vein expresses arterial phenotype in hyperhomocysteinemia. Int J Physiol Pathophysiol Pharmacol. 2011; 3(4):266-79. PMID: 22162783.
  19. Basu P, Qipshidze N, Sen U, Givvimani S, Munjal C, Mishra PK, Tyagi SC. Chronic hyperhomocysteinemia causes vascular remodelling by instigating vein phenotype in artery. Arch Physiol Biochem. 2011; 117(5):270-82. PMID: 21838575.
  20. Sen U, Givvimani S, Abe OA, Lederer ED, Tyagi SC. Cystathionine β-synthase and cystathionine γ-lyase double gene transfer ameliorate homocysteine-mediated mesangial inflammation through hydrogen sulfide generation. Am J Physiol Cell Physiol. 2011; 300(1):C155-63. PMID: 20943958.
  21. Mishra PK, Tyagi N, Sen U, Joshua IG, Tyagi SC. Synergism in hyperhomocysteinemia and diabetes: role of PPAR gamma and tempol. Cardiovasc Diabetol. 2010; 9:49. PMID: 20828387.
  22. Qipshidze N, Tyagi N, Sen U, Givvimani S, Metreveli N, Lominadze D, Tyagi SC. Folic acid mitigated cardiac dysfunction by normalizing the levels of tissue inhibitor of metalloproteinase and homocysteine-metabolizing enzymes postmyocardial infarction in mice. Am J Physiol Heart Circ Physiol. 2010; 299(5):H1484-93. PMID: 20802128.
  23. Steed MM, Tyagi N, Sen U, Schuschke DA, Joshua IG, Tyagi SC. Functional consequences of the collagen/elastin switch in vascular remodeling in hyperhomocysteinemic wild-type, eNOS-/-, and iNOS-/- mice. Am J Physiol Lung Cell Mol Physiol. 2010; 299(3):L301-11. PMID: 20581102.
  24. Sen U, Munjal C, Qipshidze N, Abe O, Gargoum R, Tyagi SC. Hydrogen sulfide regulates homocysteine-mediated glomerulosclerosis. Am J Nephrol. 2010; 31(5):442-55. PMID: 20395677.
  25. Sen U, Basu P, Abe OA, Givvimani S, Tyagi N, Metreveli N, Shah KS, Passmore JC, Tyagi SC. Hydrogen sulfide ameliorates hyperhomocysteinemia-associated chronic renal failure. Am J Physiol Renal Physiol. 2009; 297(2):F410-9. PMID: 19474193.

Review articles

  1. Gupta S, Sen U. More than just an enzyme: Dipeptidyl peptidase-4 (DPP-4) and its association with diabetic kidney remodelling. Pharmacol Res. 2019; 147:104391. PMID: 31401210.
  2. Weber GJ, Pushpakumar S, Tyagi SC, Sen U. Homocysteine and hydrogen sulfide in epigenetic, metabolic and microbiota related renovascular hypertension. Pharmacol Res. 2016;113(Pt A):300-312. PMID: 27602985.
  3. Amin M, Pushpakumar SB, Muradashvili N, Kundu S, Tyagi, SC, Sen U. Regulation and involvement of matrix metalloproteinases in vascular diseases. Frontiers in Bioscience, Front Biosci (Landmark Ed). 2016 Jan 1;21:89-118. PMID: 26709763.
  4. Pushpakumar SB, Kundu S, Sen U. Endothelial dysfunction: The link between homocysteine and hydrogen sulfide. Curr Med Chem. 2014; 21(32):3662-72. PMID: 25005183.
  5. Sen U, Pushpakumar SB, Amin MA, Tyagi SC. Homocysteine in renovascular complications: Hydrogen sulfide is a modulator and plausible anaerobic ATP generator. Nitric Oxide. 2014; 41:27-37. PMID: 24963795.

Publication Link:

http://www.ncbi.nlm.nih.gov/pubmed/?term=sen%2C+utpal+louisville