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Abstract: FR-PO355

Combination of SGLT2 Inhibition and ARB Additively Ameliorate High Glucose-Induced Epithelial-Mesenchymal Transition in HK-2 Cells

Session Information

Category: Diabetic Kidney Disease

  • 701 Diabetic Kidney Disease: Basic


  • Kim, Hyo Jeong, Gangnam Severance Hospital, Seoul, Korea (the Republic of)
  • Jhee, Jong Hyun, Gangnam Severance Hospital, Seoul, Korea (the Republic of)
  • Choi, Hoon Young, Gangnam Severance Hospital, Seoul, Korea (the Republic of)
  • Park, Hyeong cheon, Gangnam Severance Hospital, Seoul, Korea (the Republic of)

Both angiotensin receptor blocker (ARB) and sodium-glucose co-transporter 2 (SGLT2) inhibitors have renal protective effects in diabetic kidney disease; however, their synergistic effects when used in combination are not well understood.


Human kidney-2 (HK-2) cells were divided into five groups: 1) normal glucose (NG, 5.5 mM), 2) high glucose (HG, 25 mM), 3) HG + candesartan (1μM), 4) HG + dapagliflozin (10 μM), and 5) HG + candesartan + dapagliflozin combination treatment groups. The levels of epithelial-mesenchymal transition (EMT) and inflammation markers were evaluated using real time polymerase chain reaction and western blotting. The changes in the high-mobility group box-1 (HMGB1), receptor for advanced glycation end products (RAGE), and nuclear factor kappa B(NF-kB) signaling pathways were compared among the different groups.


Compared to NG, HG increased mRNA expression and proteins levels of factors associated with renal fibrosis and inflammatory response including transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), collagen type I alpha 1 chain (COL1A1), fibronectin, and tumor necrosis factor-α (TNF-α). In addition, HG decreased the expression of E-cadherin. Treatment with candesartan or dapagliflozin effectively ameliorated these changes in mRNA and protein expressions and the effect was the greatest in combination therapy. These findings suggest that combining SGLT2 inhibitor to ARB therapy holds great promise in suppressing the progression of renal fibrosis through the inhibition of EMT. In addition, the HG group exhibited increased expressions of HMGB1, RAGE, and NF-kB, and treatment with either ARB or SGLT2 inhibitor effectively reversed the upregulation of these molecules. However, combination therapy did not significantly improve HMGB1, RAGG, and NF-kB expression compared to monotherapy.


Our results suggest combining SGLT2 inhibitor to ARB is more effective than the monotherapy for preventing EMT in HG stimulated HK-2 cells.