2. Academic Validation
  3. Low dose Taxol ameliorated renal fibrosis in mice with diabetic kidney disease by downregulation of HIPK2

Low dose Taxol ameliorated renal fibrosis in mice with diabetic kidney disease by downregulation of HIPK2

  • Life Sci. 2023 Mar 11;320:121540. doi: 10.1016/j.lfs.2023.121540.
Yang Xia 1,  Hongwei Jiang 2,  Jinwen Chen 3,  Fang Xu 1,  Guoxiu Zhang 4,  Dongshan Zhang 5
Affiliations

Affiliations

  • 1 Department of Emergency Medicine, Second Xiangya Hospital, People's Republic of China; Emergency Medicine and Difficult Diseases Institute, Second Xiangya Hospital, People's Republic of China.
  • 2 Department of Endocrinology, First Affiliated Hospital of Henan University of Science and Technology, People's Republic of China.
  • 3 Department of Emergency Medicine, Hunan Aerospace Hospital, People's Republic of China.
  • 4 Department of General Practice, First Affiliated Hospital of Henan University of Science and Technology, People's Republic of China.
  • 5 Department of Emergency Medicine, Second Xiangya Hospital, People's Republic of China; Emergency Medicine and Difficult Diseases Institute, Second Xiangya Hospital, People's Republic of China; Department of General Practice, First Affiliated Hospital of Henan University of Science and Technology, People's Republic of China. Electronic address: dongshanzhang@csu.edu.cn.
PMID: 36907324 DOI: 10.1016/j.lfs.2023.121540
Abstract

Our previous studies reported that low-dose paclitaxel (Taxol) ameliorated renal fibrosis in the unilateral ureteral obstruction and remnant kidney models. However, the regulatory role of Taxol in diabetic kidney disease (DKD) is still unclear. Herein, we observed that low-dose Taxol attenuated high glucose-increased expression of fibronectin, collagen I and collagen IV in Boston University mouse proximal tubule cells. Mechanistically, Taxol suppressed the expression of homeodomain-interacting protein kinase 2 (HIPK2) via disrupting the binding of SMAD3 to HIPK2 promoter region, and consequently inhibited the activation of p53. Besides, Taxol ameliorated RF in Streptozotocin mice and db/db-induced DKD via suppression of SMAD3/HIPK2 axis as well as inactivation of p53. Altogether, these results suggest that Taxol can block Smad3-HIPK2/p53 axis, thereby attenuating the progression of DKD. Hence, Taxol is a promising therapeutic drug for DKD.

Keywords

Diabetic kidney disease; HIPK2; Smad3; Taxol; p53.

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