Journal of Traditional Chinese Medicine >
Qiteng Xiaozhuo granules (芪藤消浊颗粒) medicated serum inhibits excessive proliferation and promotes apoptosis of human glomerular mesangial cells by targeting fat mass and obesity associated proteins
Received date: 2022-09-23
Accepted date: 2022-12-24
Online published: 2023-09-01
Supported by
Lnc NONRATG001910.2 Competitively Binds miR-339 to Regulate the Mechanism of Syk Involvement in the Pathogenesis of Chronic Nephritis and the Intervention of Qiteng Xiaozhuo Particles(81973546);Study on the Mechanism of FTO-Mediated FOXO6 mRNA m6A Modification Regulating the Proliferation and Apoptosis of Glomerular Mesangial Cells(2022AH050747);Expression and Target Analysis of miR-155-5p in Kidney Tissue of CGN Rats(XLY-201912)
OBJECTIVE: To explore whether fat mass and obesity associated proteins (FTO) is an important target of Qiteng Xiaozhuo granules (QTXZG,芪藤消浊颗粒) medicated serum in regulating proliferation and apoptosis of glomerular mesangial cells.
METHODS: Medicated serum was obtained from Sprague-Dawley (SD) rats administered intragastrically with QTXZG decoction. The optimal concentration and intervention time of medicated serum were selected with the cell counting kit 8 assay. Cell proliferation was assessed by 5-ethynyl-2′-deoxyuridine (EdU) and cell apoptosis was investigated using flow cytometry. The expression of FTO, Proliferating cell nuclear antigen, Cyclin D1, B-cell lymphoma 2 (Bcl2) and BCL2 assaciated X was detected by Western blot and Real-time quantitative polymerase chain reaction, respectively. Quantification of the m6A RNA methylation was utilized to determine the total level of m6A methylation modification.
RESULTS: EdU and flow cytometry assays revealed that QTXZG medicated serum can remarkably inhibit proliferation and promote apoptosis of lipopolysaccharide (LPS)-induced human glomerular mesangial cells (HGMCs). The FTO overexpression plasmid could inhibit proliferation and promote apoptosis of LPS-induced HGMCs. The FTO inhibitor (FB23-2) can significantly attenuate the effect of QTZXG medicated serum on inhibiting excessive proliferation and promoting apoptosis. QTXZG medicated serum can significantly increase FTO expression and decrease the level of m6A methylation modification.
CONCLUSIONS: FTO is a key target for QTXZG medicated serum in inhibiting excessive proliferation and promoting apoptosis of human glomerular mesangial cells.
Xingxing ZHUANG , Tao LIU , Liangbing WEI , Junmei SONG , Jiarong GAO . Qiteng Xiaozhuo granules (芪藤消浊颗粒) medicated serum inhibits excessive proliferation and promotes apoptosis of human glomerular mesangial cells by targeting fat mass and obesity associated proteins[J]. Journal of Traditional Chinese Medicine, 2023 , 43(6) : 1072 -1080 . DOI: 10.19852/j.cnki.jtcm.2023.06.005
| 1. | Wei LB, Gao JR, Gao YC, Liu XC, Jiang H, Qin XJ. Effect of the Traditional Chinese Medicine Qiteng Xiaozhuo granules on chronic glomerulonephritis rats studied by using long noncoding RNAs expression profiling. Gene 2020; 728: 144279. |
| 2. | Gao JR, Jiang NN, Jiang H, et al. Effects of Qiteng Xiaozhuo granules on circRNA expression profiles in rats with chronic glomerulonephritis. Drug Des Devel Ther 2019; 13: 1901-13. |
| 3. | Gao JR, Qin XJ, Jiang H, Wang T, Song JM, Xu SZ. The effects of Qiteng Xiaozhuo granules, Traditional Chinese Medicine, on the expression of genes in chronic glomerulonephritis rats. J Ethnopharmacol 2016; 193: 140-9. |
| 4. | Liu T, Gao YC, Qin XJ, Gao JR. Exploring the mechanism of Jianpi Qushi Huayu formula in the treatment of chronic glomerulonephritis based on network pharmacology. Naunyn Schmiedebergs Arch Pharmacol 2021; 394: 2451-70. |
| 5. | Avraham S, Korin B, Chung JJ, Oxburgh L, Shaw AS. The mesangial cell-the glomerular stromal cell. Nat Rev Nephrol 2021; 17: 855-64. |
| 6. | Kurogi Y. Mesangial cell proliferation inhibitors for the treatment of proliferative glomerular disease. Med Res Rev 2003; 23: 15-31. |
| 7. | Tsuboi N, Utsunomiya Y, Kawamura T, et al. Shedding of growth-suppressive gangliosides from glomerular mesangial cells undergoing apoptosis. Kidney Int 2003; 63: 936-46. |
| 8. | Scindia YM, Deshmukh US, Bagavant H. Mesangial pathology in glomerular disease: targets for therapeutic intervention. Adv Drug Deliv Rev. 2010; 62: 1337-43. |
| 9. | Wu L, Li O, Zhu F, et al. Kr?ppel-like factor 15 suppresses renal glomerular mesangial cell proliferation via enhancing P53 SUMO1 conjugation. J Cell Mol Med 2021; 25: 5691-706. |
| 10. | Shan HJ, Gu WX, Duan G, Chen HL. Fat mass and obesity associated (FTO)-mediated N6-methyladenosine modification of Krüppel-like factor 3 (KLF3) promotes osteosarcoma progression. Bioengineered 2022; 13: 8038-50. |
| 11. | Yang X, Mei C, Ma X, Du J, Wang J, Zan L. m6A methylases regulate myoblast proliferation, apoptosis and differentiation. Animals (Basel) 2022; 12: 773. |
| 12. | Zhuang XX, Zhou L, Miao RH, Ni SD, Li M. Pharmacokinetic interaction between Asari Radix et Rhizoma and Dried Ginger (Zingiber officinalis) in rats. Curr Pharm Analy 2022; 18: 63-70. |
| 13. | Liu T, Zhuang XX, Qin XJ, Wei LB, Gao JR. Alteration of N6-methyladenosine epitranscriptome profile in lipopolysaccharide-induced mouse mesangial cells. Naunyn Schmiedebergs Arch Pharmacol 2022; 395: 445-58. |
| 14. | Lee IT, Shih RH, Lin CC, Chen JT, Yang CM. Role of TLR4/NADPH oxidase/ROS-activated p38 MAPK in VCAM-1 expression induced by lipopolysaccharide in human renal mesangial cells. Cell Commun Signal 2012; 10: 33. |
| 15. | Chao S, Xu Q, Dong S, Guo M, Liu X, Cheng X. Polygala fallax Hemsl combined with compound Sanqi granules relieves glomerulonephritis by regulating proliferation and apoptosis of glomerular mesangial cells. J Int Med Res 2020; 48: 300060519894124. |
| 16. | Huang Y, Su R, Sheng Y, et al. Small-molecule targeting of oncogenic FTO demethylase in acute myeloid leukemia. Cancer Cell 2019; 35: 677-91. |
| 17. | Jia G, Fu Y, Zhao X, et al. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol 2011; 7: 885-7. |
| 18. | Zhao X, Yang Y, Sun BF, et al. FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis. Cell Res 2014; 24: 1403-19. |
| 19. | Niu Y, Lin Z, Wan A, et al. RNA N6-methyladenosine demethylase FTO promotes breast tumor progression through inhibiting BNIP3. Mol Cancer 2019; 18: 46. |
| 20. | Wani SM, Gani A, Mir SA, Masoodi FA, Khanday FA. β-Glucan: a dual regulator of apoptosis and cell proliferation. Int J Biol Macromol 2021; 182: 1229-37. |
| 21. | Ye K, Wei Q, Gong Z, et al. Effect of norcantharidin on the proliferation, apoptosis, and cell cycle of human mesangial cells. Ren Fail 2017; 39: 458-64. |
| 22. | Zhang CJ, Zhao D, Yin X, et al. Effects of 1,25(OH)2D3 on proliferation and apoptosis of human glomerular mesangial cells. Am J Transl Res 2016; 8: 2659-66. |
| 23. | Liang X, Xu W. miR-181a-5p regulates the proliferation and apoptosis of glomerular mesangial cells by targeting KLF6. Exp Ther Med 2020; 20: 1121-8. |
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