Shensu IV prevents glomerular podocyte injury in nephrotic rats via promoting lncRNA H19/DIRAS3-mediated autophagy
| Autor: | Chanjun Wan, Maohong Wang, Guoqing Wu, Chiheng Pi, Weiguo Song, Yaqian Huang, Yehua Zhou, Yong Huang, Jie Cheng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male rho GTP-Binding Proteins medicine.medical_specialty Cell Homeostasis & Autophagy autophagy Biophysics Biochemistry Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound podocyte damage 0302 clinical medicine Endocrinology Internal medicine Shensu IV medicine Choline Tetramethylpyrazine Animals Molecular Biology Pathological PI3K/AKT/mTOR pathway Research Articles Cells Cultured Kidney Podocytes TOR Serine-Threonine Kinases Autophagy Cell Biology Therapeutics & Molecular Medicine Rats 030104 developmental biology medicine.anatomical_structure lncRNA H19 chemistry Puromycin 030220 oncology & carcinogenesis DIRAS3 Nephrosis RNA Long Noncoding Microtubule-Associated Proteins Drugs Chinese Herbal |
| Zdroj: | Bioscience Reports |
| ISSN: | 1573-4935 0144-8463 |
| Popis: | Shensu IV is a Chinese prescription well-known for its function in treating chronic kidney diseases. However, the potential mechanisms underlying how Shensu IV exerts its effects remain unclear. In the present study, we investigated the effects of Shensu IV on glomerular podocyte injury in nephrotic rats and puromycin-induced injury in cultured podocytes, and assessed the associated molecular mechanisms. Liquid chromatography–mass spectrometry (LC–MS) results showed that the main components of Shensu IV were l-Carnitine, P-lysoPC (LPC) 16:0, Coumaroyl tyramine, Tetramethylpyrazine, LPC 18:1, Choline, (S,S)-Butane-2,3-diol, and Scopoletin. We further found that nephrotic rats displayed pathological alterations in kidney tissues and ultrastructural changes in glomerular podocytes; however, these effects were reversed with Shensu IV treatment. Compared with the control, the numbers of autophagosomes were markedly reduced in the model group, but not in the Shensu IV treatment group. Furthermore, the expression of p62 was significantly higher in the model group than in the controls, whereas the LC3-II/I ratio was significantly lower; however, these changes were not observed when Shensu IV was administered. The protective effects of Shensu IV were further confirmed in podocytes displaying puromycin-induced injury. Compared with control group, the expression of long non-coding RNA (lncRNA) H19, mTOR, p-mTOR, and p62 was significantly increased in the puromycin group, whereas that of distinct subgroup of the RAS family member 3 (DIRAS3) was significantly decreased, as was the LC3-II/I ratio. The opposite results were obtained for both shH19- and Shensu IV-treated cells. Collectively, our data demonstrated that Shensu IV can prevent glomerular podocyte injury in nephrotic rats and puromycin-treated podocytes, likely via promoting lncRNA H19/DIRAS3-regulated autophagy. |
| Databáze: | OpenAIRE |
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