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

 

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

Renovascular 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 impairment of renal function. Finding the mechanisms of renal remodeling during the above-mentioned disease conditions will enable us to design strategies to mitigate or prevent renal disease progression in hypertension and diabetes.


Recent publications: selected from more than 85 peer-reviewed articles

Research articles  

  1. Majumder S, Pushpakumar S, Juin SK, Jala VR, Sen U. Toll-like receptor 4 mutation protects the kidney from Ang-II-induced hypertensive injury. Pharmacol Res. 2022; 175:106030. PMID: 34896544
  2. Juin SK, Pushpakumar S, Sen U. GYY4137 regulates extracellular matrix turnover in the diabetic kidney by modulating retinoid X receptor signaling. Biomolecules, 2021; 11(10):1477. PMID: 34680110
  3. Pushpakumar S, Kundu S, Weber G, Sen U. Exogenous hydrogen sulfide and miR-21 antagonism attenuates macrophage-mediated inflammation in ischemia reperfusion injury of the aged kidney. Geroscience, 2021; 43(3):1349-1367. PMID: 33433751
  4. Pushpakumar S, Ren L, Juin SK, Majumder S, Kulkarni R, Sen U. Methylation-dependent antioxidant-redox imbalance regulates hypertensive kidney injury in aging. Redox Biol, 2020, 37: 101754. PMID: 33080442
  5. Majumder S, Amin M, Pushpakumar S, Sen U. Collagen receptor- and metalloproteinase-dependent hypertensive stress response in mesangial and glomerular endothelial cells. Mol Cell Biochem. 2020; 466 (1-2): 1-15. PMID: 31912277
  6. 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. Cell Signal. 2019; 61:66-77. PMID: 31085234
  7. 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
  8. 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 
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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.
  14. 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.
  15. 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.
  16. 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.   
  17. 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.
  18. 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.
  19. 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.
  20. 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.

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: 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; 21:89-118. PMID: 26709763.
  4. Pushpakumar S, 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.