Low dose Taxol ameliorated renal fibrosis in mice with diabetic kidney disease by downregulation of HIPK2
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...
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Veröffentlicht in: | Life sciences (1973) 2023-05, Vol.320, p.121540-121540, Article 121540 |
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Sprache: | eng |
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Zusammenfassung: | 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.
The anti-fibrosis molecular mechanism of low-dose Taxol. Low-dose Taxol suppressed the activation of Smad3 and inhibited the binding of Smad3 to HIPK2 PR, and then prevented HG-induced renal fibrosis. (SMAD3: Smad family member 3, HIPK2: Homeodomain-interacting protein kinase 2). [Display omitted] |
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ISSN: | 0024-3205 1879-0631 |
DOI: | 10.1016/j.lfs.2023.121540 |