GSK-3β在泌尿系结石形成机制中的作用研究进展

陈策; 木拉提·马合木提

doi:10.13201/j.issn.1001-1420.2022.11.017

GSK-3β在泌尿系结石形成机制中的作用研究进展

陈策¹,
木拉提·马合木提^1, ,

- 新疆医科大学第二附属医院泌尿外科(乌鲁木齐，830036)
基金项目:
国家自然科学基金(No：81760128)

详细信息

通讯作者: 木拉提·马合木提，E-mail：mekit@126.com

中图分类号: R691.4

收稿日期: 2021-12-14

刊出日期: 2022-11-06

Role of GSK-3β in the formation mechanism of urinary stones

CHEN Ce¹,
Mulati· Mahemuti^1, ,

- Department of Urology, Second Affiliated Hospital of Xinjiang Medical University, Urumqi, 830036, China

More Information

Corresponding author: Mulati·Mahemuti, E-mail: mekit@126.com

Received Date: 14 December 2021

Publish Date: 06 November 2022

摘要

摘要: 糖原合成酶激酶-3β(GSK-3β)是一种在睾丸、胸腺、卵巢、肺、脑以及肾脏等组织广泛表达的活性丝氨酸/苏氨酸激酶，通过多种信号途径使细胞底物磷酸化，从而调节多种细胞功能，包括发育、代谢、基因转录、蛋白翻译、细胞骨架组织、细胞周期调控和凋亡等。大量研究发现，GSK-3β在氧化应激中发挥着重要的调控作用，而氧化应激是泌尿系结石的发展中起关键作用之一。本文就GSK-3β在泌尿系结石形成机制中的研究进展作一综述。
- GSK-3β /
- 泌尿系结石 /
- 氧化应激 /
- Nrf2信号通路
Abstract: Glycogen synthase kinase-3 beta(GSK-3β) is an active serine/threonine kinase widely expressed in the testicles, thymus, ovaries, lungs, brain, and kidneys, which phosphorylates the cell substrate through a variety of signaling pathways, thereby regulating a variety of cellular functions, including development, metabolism, gene transcription, protein translation, cytoskeletal tissue, cell cycle regulation and apoptosis. A large number of studies have found that GSK-3 beta plays an important regulatory role in oxidative stress, which plays a key role in the development of urinary stones. Therefore, this paper summarizes the research progress of GSK-3β in the formation mechanism of urinary stones.
- GSK-3β /
- urinary stones /
- oxidative stress /
- Nrf2 signaling pathway

HTML全文

图 1 GSK-3β调节mPTP开放的机制

下载: 全尺寸图片幻灯片

图 2 GSK-3β调节Nrf2信号通路的机制

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参考文献(39)

[1]	Zeng G, Mai Z, Xia S, et al. Prevalence of kidney stones in China: an ultrasonography based cross-sectional study[J]. BJU Int, 2017, 120(1): 109-116. doi: 10.1111/bju.13828
[2]	Wang Z, Zhang Y, Zhang J, et al. Recent advances on the mechanisms of kidney stone formation(Review)[J]. Int J Mol Med, 2021, 48(2): 149. doi: 10.3892/ijmm.2021.4982
[3]	Kandar CC, Sen D, Maity A. Anti-inflammatory potential of GSK-3 inhibitors[J]. Curr Drug Targets, 2021, 22(13): 1464-1476. doi: 10.2174/1389450122666210118150313
[4]	Cormier KW, Woodgett JR. Recent advances in understanding the cellular roles of GSK-3[J]. F1000Res, 2017, 6: F1000 Faculty Rev-167.
[5]	Robertson H, Hayes JD, Sutherland C. A partnership with the proteasome; the destructive nature of GSK3[J]. Biochem Pharmacol, 2018, 147: 77-92. doi: 10.1016/j.bcp.2017.10.016
[6]	Yang K, Chen Z, Gao J, et al. The key roles of GSK-3β in regulating mitochondrial activity[J]. Cell Physiol Biochem, 2017, 44(4): 1445-1459. doi: 10.1159/000485580
[7]	董新岩, 任珺, 盛建中. GSK-3β在相关疾病中的作用及致病机制的研究进展[J]. 生理科学进展, 2018, 49(2): 5. https://www.cnki.com.cn/Article/CJFDTOTAL-SLKZ201802002.htm
[8]	Chethan S, Shanthi S, Freeman ML, et al. Inhibition of GSK-3β restores delayed gastric emptying in obesity-induced diabetic female mice[J]. Am J Physiol Gastrointest Liver Physiol, 2020, 319: G481-G493. doi: 10.1152/ajpgi.00227.2020
[9]	Yasui T, Okada A, Hamamoto S, et al. Pathophysiology-based treatment of urolithiasis[J]. Int J Urol, 2017, 24(1): 32-38. doi: 10.1111/iju.13187
[10]	崔建伟, 白云金, 尹山, 等. 含钙尿路结石病单核苷酸多态性研究进展[J]. 临床泌尿外科杂志, 2021, 36(8): 657-662, 667. doi: 10.13201/j.issn.1001-1420.2021.08.014
[11]	江绍钦, 李梦强, 陈珍霖, 等. 氯喹抑制高糖环境下前列腺癌PC3细胞增殖机制研究[J]. 临床泌尿外科杂志, 2021, 36(1): 46-50. doi: 10.13201/j.issn.1001-1420.2021.01.010
[12]	Millare B, O'Rourke B, Trayanova N. Hydrogen peroxide diffusion and scavenging shapes mitochondrial network instability and failure by sensitizing ROS-induced ROS release[J]. Sci Rep, 2020, 10(1): 15758. doi: 10.1038/s41598-020-71308-z
[13]	Müller M, Ahumada-Castro U, Sanhueza M, et al. Mitochondria and calcium regulation as basis of neurodegeneration associated with aging[J]. Front Neurosci, 2018, 12: 470. doi: 10.3389/fnins.2018.00470
[14]	Liu D, Yu H, Gao L, et al. The inhibition of GSK-3β promotes the production of reactive oxygen species via β-catenin/C/EBPα signaling in the spleen of zebrafish(Danio rerio)[J]. Fish Shellfish Immunol, 2018, 76: 110-120. doi: 10.1016/j.fsi.2018.02.040
[15]	Zeng X, Xi Y, Jiang W. Protective roles of flavonoids and flavonoid-rich plant extracts against urolithiasis: A review[J]. Crit Rev Food Sci Nutr, 2019, 59(13): 2125-2135. doi: 10.1080/10408398.2018.1439880
[16]	Wang M, Liu Y, Pan RL, et al. Protective effects of Myricarubra flavonoids against hypoxia/reoxygenation-induced cardiomyocyte injury via the regulation of the PI3K/Akt/GSK3β pathway[J]. Int J Mol Med, 2019, 43(5): 2133-2143.
[17]	Shin JH, Kim KM, Jeong JU, et al. Nrf2-heme oxygenase-1 attenuates high-glucose-induced epithelial-to-mesenchymal transition of renal tubule cells by inhibiting ROS-mediated PI3K/Akt/GSK-3βsignaling[J]. J Diabetes Res, 2019: 2510105.
[18]	Li C, Ge Y, Dworkin L, et al. The β isoform of GSK3 mediates podocyte autonomous injury in proteinuric glomerulopathy[J]. J Pathol, 2016, 239(1): 23-35. doi: 10.1002/path.4692
[19]	Theeuwes WF, Gosker HR, Schols AMWJ, et al. Regulation of PGC-1α expression by a GSK-3β-TFEB signaling axis in skeletal muscle[J]. Biochim Biophys Acta Mol Cell Res, 2020, 1867(2): 118610. doi: 10.1016/j.bbamcr.2019.118610
[20]	Undi RB, Gutti U, Gutti RK. LiCl regulates mitochondrial biogenesis during megakaryocyte development[J]. J Trace Elem Med Biol, 2017, 39: 193-201. doi: 10.1016/j.jtemb.2016.10.003
[21]	Geto Z, Molla MD, Challa F, et al. Mitochondrial dynamic dysfunction as a main triggering factor for inflammation associated chronic non-communicable diseases[J]. J Inflamm Res, 2020, 13: 97-107. doi: 10.2147/JIR.S232009
[22]	周丽洁. 猴头菌素通过抑制人肝细胞癌PI3K/Akt/GSK-3β信号通路诱导线粒体膜通透性转移孔开放[D]. 华北理工大学, 2020.
[23]	Jin FJ, Wu ZZ, Hu X, et al. The PI3K/Akt/GSK-3β/ROS/eIF2B pathway promotes breast cancer growth and metastasis via suppression of NK cell cytotoxicity and tumor cell susceptibility[J]. Cancer Biol Med, 2019, 16(1): 38-54. doi: 10.20892/j.issn.2095-3941.2018.0253
[24]	Vélez DE, Mestre-Cordero VE, Hermann R, et al. Rosuvastatin protects isolated hearts against ischemia-reperfusion injury: role of Akt-GSK-3β, metabolic environment, and mitochondrial permeability transition pore[J]. J Physiol Biochem, 2020, 76(1): 85-98. doi: 10.1007/s13105-019-00718-z
[25]	Wang C, Cai ZX, Wang W, et al. Piperine regulates glycogen synthase kinase-3β-related signaling and attenuates cognitive decline in D-galactose-induced aging mouse model[J]. J Nutr Biochem, 2020, 75: 108261. doi: 10.1016/j.jnutbio.2019.108261
[26]	Li ZG, Zhu HF, Liu C, et al. GSK-3β inhibition protects the rat heart from the lipopolysaccharide-induced inflammation injury via suppressing FOXO3A activity[J]. J Cell Mol Med, 2019, 23(11): 7796-7809. doi: 10.1111/jcmm.14656
[27]	Ranea-Robles P, Launay N, Ruiz M, et al. Aberrant regulation of the GSK-3β/NRF2 axis unveils a novel therapy for adrenoleukodystrophy[J]. EMBO Mol Med, 2018, 10(8): e8604.
[28]	Tu W, Wang H, Li S, et al. The anti-inflammatory and anti-oxidant mechanisms of the Keap1/Nrf2/ARE signaling pathway in chronic diseases[J]. Aging Dis, 2019, 10(3): 637-651. doi: 10.14336/AD.2018.0513
[29]	Renaud CO, Ziros PG, Chartoumpekis DV, et al. Keap1/Nrf2 signaling: a new player in thyroid pathophysiology and thyroid cancer[J]. Front Endocrinol, 2019, 10: 510. doi: 10.3389/fendo.2019.00510
[30]	Ren ZL, Zhong H, Song CC, et al. Insulin promotes mitochondrial respiration and survival through PI3K/AKT/GSK3 pathway in human embryonic stem cells[J]. Stem Cell Reports, 2020, 15(6): 1362-1376. doi: 10.1016/j.stemcr.2020.10.008
[31]	Li Y, Chu L, Liu CF, et al. Protective effect of GSK-3β/Nrf2 mediated by dimethyl fumarate in middle cerebral artery embolization reperfusion rat model[J]. Curr Neurovasc Res, 2021, 18(4): 456-464. doi: 10.2174/1567202618666211109105024
[32]	Silva-Palacios A, Ostolga-Chavarría M, Zazueta C, et al. Nrf2: Molecular and epigenetic regulation during aging[J]. Ageing Res Rev, 2018, 47: 31-40. doi: 10.1016/j.arr.2018.06.003
[33]	Zhang J, Lai ZP, Chen P, et al. Glycogen synthase kinase-3β inhibitor SB216763 promotes DNA repair in ischemic retinal neurons[J]. Neural Regen Res, 2021, 16(2): 394-400. doi: 10.4103/1673-5374.290913
[34]	Fang Y, Zhao Y, He S, et al. Overexpression of FGF19 alleviates hypoxia/reoxygenation-induced injury of cardiomyocytes by regulating GSK-3β/Nrf2/ARE signaling[J]. Biochem Biophys Res Commun, 2018, 503(4): 2355-2362. doi: 10.1016/j.bbrc.2018.06.161
[35]	Shen XH, Hu B, Xu GT, et al. Activation of Nrf2/HO-1 pathway by glycogen synthase kinase-3β inhibition attenuates renal ischemia/reperfusion injury in diabetic rats[J]. Kidney Blood Press Res, 2017, 42(2): 369-378. doi: 10.1159/000477947
[36]	Lu M, Wang P, Qiao Y, et al. GSK3β-mediated Keap1-independent regulation of Nrf2 antioxidant response: A molecular rheostat of acute kidney injury to chronic kidney disease transition[J]. Redox Biol, 2019, 26: 101275. doi: 10.1016/j.redox.2019.101275
[37]	陈攀, 刘冬冬, 李哲铭, 等. 草酸钙结石与氧化应激相关性的研究进展[J]. 江苏医药, 2021, 47(1): 5. https://www.cnki.com.cn/Article/CJFDTOTAL-YIYA202101023.htm
[38]	Zeng X, Xi Y, Jiang W. Protective roles of flavonoids and flavonoid-rich plant extracts against urolithiasis: A review[J]. Crit Rev Food Sci Nutr, 2019, 59(13): 2125-2135. doi: 10.1080/10408398.2018.1439880
[39]	Ergul AB, Kara M, Karakukcu C, et al. High doses of boron have no protective effect against nephrolithiasis or oxidative stress in a rat model[J]. Biol Trace Elem Res, 2018, 186(1): 218-225. doi: 10.1007/s12011-018-1294-1