Tanshinone I improves renal fibrosis by promoting gluconeogenesis through upregulation of peroxisome proliferator-activated receptor-γ coactivator 1α
| Autor: | Yanfang Bai, Hui Wen, Junyan Lin, Xinying Liu, Hua Yu, Ming Wu, Ling Wang, Dongping Chen |
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| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Předmět: | |
| Zdroj: | Renal Failure, Vol 46, Iss 2 (2024) |
| Druh dokumentu: | article |
| ISSN: | 0886022X 1525-6049 0886-022X |
| DOI: | 10.1080/0886022X.2024.2433710 |
| Popis: | Background Renal fibrosis, a hallmark of chronic kidney disease, is closely associated with dysregulated gluconeogenesis. Tanshinone I (Tan I), a bioactive compound derived from the traditional Chinese medicine Danshen, exhibits antifibrotic and anti-inflammatory properties. However, its effects on gluconeogenesis and the mechanisms through which it alleviates renal fibrosis remain unclear. This study aimed to investigate whether Tan I promotes gluconeogenesis and mitigates renal fibrosis.Methods Both in vivo and in vitro experiments were conducted. A unilateral ureteral obstruction (UUO) mouse model was used. Masson’s trichrome, HE, and immunofluorescence staining, along with Western blotting, were employed. Lactate concentrations and a pyruvate tolerance test were conducted to assess glucose metabolism. In vitro, HK2 cells and primary renal tubular cells were treated with transforming growth factor-β (TGFβ) to induce fibrosis, and the effects of Tan I on glucose and lactate levels were examined.Results In the UUO model, Tan I reduced fibrosis, decreased lactate accumulation, and modulated fibrosis markers while upregulating gluconeogenesis markers. Tanshinone I restored impaired renal gluconeogenesis, as evidenced by increased pyruvate levels. In vitro, Tan I inhibited fibrosis, reduced lactate levels, and increased glucose levels in cell supernatants. It also restored gluconeogenesis protein expression and decreased fibrotic protein levels. Peroxisome proliferator-activated receptor-γ coactivator (PGC1α) expression was downregulated in UUO and TGFβ-stimulated models, and Tan I reversed this downregulation. Inhibition of PGC1α in TGFβ-stimulated cells counteracted the antifibrotic and gluconeogenesis-promoting effects of Tan I.Conclusions Tanshinone I ameliorated renal fibrosis by enhancing gluconeogenesis through upregulation of PGC1α. |
| Databáze: | Directory of Open Access Journals |
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