- Epigenetic regulation: Does HDAC2 plays role in drug resistance via regulation of P-gp and MRP-1
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Rashmika Singh,Harshit Singh,Saurabh Chaturvedi,Vikas Agarwal,Narayan Prasad
2022 ; 2022(1):
- 논문분류 :
- 춘계학술대회 초록집
Objectives: To evaluate the effect HDAC 2 on P-gp and MRP-1 expression.
Methods: 25 steroid sensitive nephrotic syndrome (SSNS), and 10 steroid resistant nephrotic syndrome (SRNS) patients were recruited in the study. mRNA expression was analyzed on peripheral blood mononuclear cells (PBMCs) in SRNS patients (mean age 8.43±3.8 years), SSNS patients (mean age 7.54±3.5 years). PBMCs were treated with 1µM of Theophylline (HDAC2 stimulator) and 0.8µM of Trichostatin A (HDAC2 inhibitor) for a period of 48 hours. qPCR was performed relative gene expression levels were calculated and normalized to the corresponding levels of the housekeeping gene (GAPDH).
Results: Expression of P-gp (4.79±0.10 v/s 2.13±0.12, p<0.0001) and MRP-1 (3.99 ±0.08 v/s 1.99 ±0.11, p<0.0001) on PBMCs was increased in SRNS as compared to that of SSNS. HDAC2 mRNA levels were significantly decreased in SRNS patients as compared to that of SSNS patients (2.97 ± 0.15 v/s 6.02 ± 0.13, p<0.0001). Theophylline for a period of 48 hours decreased mRNA levels of P-gp and MRP-1 in PBMCs of SRNS with maximal induction at 1µM (fold change 2.65 and 2.21, *p<0.0001) However HDAC2 mRNA expression increased significantly (fold change5.67, *p<0.0001). In SSNS patients P-gp and MRP-1 mRNA expression decreased at1µM (fold change 1.25, 1.24, *p<0.0001) while the mRNA expression was increased (fold change 6.93, *p<0.0001). TSA for a period of 48 hours increased mRNA levels of P-gp and MRP-1 in PBMCs of SRNS with maximal induction at 0.8µM (fold change 7.51, 7.31, *p<0.0001) and significantly decreased the level of HDAC2 (fold change1.50, *p<0.0001) similarly in SSNS patients P-gp and MRP-1 mRNA expression increased at 0.8µM (fold change 3.49, 3.35, *p<0.0001) and HDAC2 decreased (fold change2.53, *p<0.0001) at 0.8µM.
Conclusions: we observed that HDAC2 regulates P-gp and MRP-1 efflux pumps, Inducer of HDAC2 may be a probable treatment stratergy for patients of INS.