Open Access

Ginkgo biloba leaf extract prevents diabetic nephropathy through the suppression of tissue transglutaminase

  • Authors:
    • Xiaoyan Yu
    • Qing Su
    • Jianan Geng
    • Hui Liu
    • Yumeng Liu
    • Jinming Liu
    • Yan Shi
    • Yinggang Zou
  • View Affiliations

  • Published online on: February 8, 2021     https://doi.org/10.3892/etm.2021.9764
  • Article Number: 333
  • Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the preventive effects of Ginkgo biloba leaf extract (GBE) against extracellular matrix (ECM) accumulation in a streptozotocin (STZ)‑induced rat model of diabetic nephropathy (DN), and to determine its underlying molecular mechanism. In vivo, a rat model of DN was established by intraperitoneal injection of STZ, and the rats were subsequently administered GBE. The results demonstrated that GBE significantly decreased blood glucose, the urine protein excretion rate and ECM accumulation in DN rats. In addition, the development of DN significantly induced tissue transglutaminase (tTG) protein expression, which was detected by immunohistochemistry, western blotting and PCR analyses, while GBE administration decreased tTG expression in the diabetic kidney. In vitro, rat glomerular mesangial cells (HBZY‑1 cells) cultured with high glucose were also treated with GBE. The concentrations of tTG, fibronectin, type IV collagen, transforming growth factor (TGF)‑β and connective tissue growth factor (CTGF) were detected via ELISA. The results demonstrated that GBE notably decreased the concentration of these proteins, and tTG expression was positively associated with TGF‑β. GBE also suppressed tTG expression of high glucose‑treated HBZY‑1 cells in a concentration‑dependent manner. Furthermore, tTG protein expression was detected in high glucose‑treated HBZY‑1 cells transfected with small interfering RNA (siRNA) oligonucleotides against TGF‑β and CTGF to investigate a possible mechanism of GBE‑mediated inhibition of tTG. The results demonstrated that the tTG levels remained unchanged in CTGF siRNA‑transfected cells, but were decreased in the GBE + CTGF siRNA group compared with the control siRNA group, suggesting that tTG may not be regulated by CTGF, and the inhibitory effect of GBE on tTG may not be associated with the direct inhibition of CTGF. However, tTG expression was decreased following the transfection with TGF‑β siRNA, in which levels of tTG were similar compared with both the GBE group and GBE + TGF‑β siRNA group, indicating that tTG may be regulated by TGF‑β, and that the GBE‑induced repression of tTG expression may be associated with the downregulation of TGF‑β. Taken together, the results of the present study suggest that GBE prevented ECM accumulation by suppressing tTG expression in DN, which was predominantly mediated by TGF‑β.
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April-2021
Volume 21 Issue 4

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Spandidos Publications style
Yu X, Su Q, Geng J, Liu H, Liu Y, Liu J, Shi Y and Zou Y: <em>Ginkgo biloba</em> leaf extract prevents diabetic nephropathy through the suppression of tissue transglutaminase. Exp Ther Med 21: 333, 2021
APA
Yu, X., Su, Q., Geng, J., Liu, H., Liu, Y., Liu, J. ... Zou, Y. (2021). <em>Ginkgo biloba</em> leaf extract prevents diabetic nephropathy through the suppression of tissue transglutaminase. Experimental and Therapeutic Medicine, 21, 333. https://doi.org/10.3892/etm.2021.9764
MLA
Yu, X., Su, Q., Geng, J., Liu, H., Liu, Y., Liu, J., Shi, Y., Zou, Y."<em>Ginkgo biloba</em> leaf extract prevents diabetic nephropathy through the suppression of tissue transglutaminase". Experimental and Therapeutic Medicine 21.4 (2021): 333.
Chicago
Yu, X., Su, Q., Geng, J., Liu, H., Liu, Y., Liu, J., Shi, Y., Zou, Y."<em>Ginkgo biloba</em> leaf extract prevents diabetic nephropathy through the suppression of tissue transglutaminase". Experimental and Therapeutic Medicine 21, no. 4 (2021): 333. https://doi.org/10.3892/etm.2021.9764