
浏览全部资源
扫码关注微信
401120 重庆,重庆医科大学附属第三医院心血管内科
[司良毅,E-mail:650273@hospital.cqmu.edu.cn SI Liangyi, E-mail: 650273@hospital.cqmu.edu.cn
收稿:2023-05-30,
修回:2023-06-22,
纸质出版:2023-11-15
移动端阅览
唐刚, 王维维, 钟理, 等. 转录因子FLI-1通过上调Klotho基因改善心肌细胞肥大[J]. 陆军军医大学学报, 2023,45(21):2231-2238.
Gang TANG, Weiwei WANG, Li ZHONG, et al. FLI-1 ameliorates cardiac hypertrophy by inhibiting IGF-1R/Gi/PLC pathway
唐刚, 王维维, 钟理, 等. 转录因子FLI-1通过上调Klotho基因改善心肌细胞肥大[J]. 陆军军医大学学报, 2023,45(21):2231-2238. DOI: 10.16016/j.2097-0927.202305112.
Gang TANG, Weiwei WANG, Li ZHONG, et al. FLI-1 ameliorates cardiac hypertrophy by inhibiting IGF-1R/Gi/PLC pathway
目的
2
探讨转录因子FLI-1通过Klotho介导的IGF-1R/Gi/PLC途径对心肌细胞肥大的影响。
方法
2
将大鼠心肌细胞(H9c2)分为对照组、模型组、模型+NC Vector组、模型+pcDNA-FLI-1组、模型+NC Vector+NC siRNA组、模型+NC Vector+Klotho siRNA组、模型+pcDNA-FLI-1+NC siRNA组和模型+pcDNA-FLI-1+Klotho siRNA组等共8组。通过用异丙肾上腺素(isoproterenol,ISO)处理细胞,建立心肌细胞肥大模型,细胞分别转染pcDNA-FLI-1和Klotho siRNA。采用流式细胞术观测细胞凋亡,鬼笔环肽染色观测细胞肥大面积;采用Western blot检测细胞凋亡、肥大及IGF-1R/Gi/PLC途径相关蛋白的表达。
结果
2
与对照组比较,模型组细胞凋亡率、心肌细胞表面积及IGF-1R、GNAI1和PLCG1表达显著增加(
P
<
0.05),表明建模成功;与模型+NC Vector组比较,模型+pcDNA-FLI-1组细胞凋亡、心肌细胞表面积及IGF-1R、GNAI1和PLCG1表达显著降低(
P
<
0.05)。与模型+NC Vector+NC siRNA组相比,模型+NC Vector+Klotho siRNA组细胞凋亡、心肌细胞表面积及IGF-1R、GNAI1和PLCG1表达显著增加(
P
<
0.05);与模型+pcDNA-FLI-1+NC siRNA组相比,模型+pcDNA-FLI-1+Klotho siRNA组细胞凋亡、心肌细胞表面积及IGF-1R、GNAI1和PLCG1表达显著降低(
P
<
0.05)。
结论
2
FLI-1能够通过上调Klotho抑制IGF-1R/Gi/PLC途径,减轻心肌细胞凋亡及心肌细胞肥大面积。
Objective
2
To investigate the effect of FLI-1 on Klotho-mediated IGF-1R/Gi/PLC pathway on cardiomyocyte hypertrophy.
Methods
2
The cells were divided into 8 groups: control group
model group
model+NC Vector group
model+pcDNA-FLI-1 group
model+NC Vector+NC siRNA group
model+NC Vector+Klotho siRNA group
model+pcDNA-FLI-1+NC siRNA group and model+pcDNA-FLI-1+Klotho siRNA group. Cardiomyocyte hypertrophy models were established by treating cells with isoproterenol (ISO)
and the latter cells were transfected with pcDNA-FLI-1 and Klotho siRNA
respectively. Apoptosis was detected by flow cytometry; hypertrophic area was detected by phalloidin staining; apoptosis
hypertrophy and expression of IGF-1R/Gi/PLC pathway-related proteins were detected by Western blotting.
Results
2
Compared with the control group
the ISO group had increased apoptotic rate
cardiomyocyte surface area and IGF-1R
GNAI1 and PLCG1 expression
indicating successful modeling; compared with the model +NC Vector group
the model +pcDNA-FLI-1 group had decreased apoptosis
cardiomyocyte surface area and IGF-1R
GNAI1 and PLCG1 expression. Apoptosis
cardiomyocyte surface area
and IGF-1R
GNAI1 and PLCG1 expression were increased in the model +NC Vector+Klotho siRNA group compared with the model +NC Vector+NC siRNA group; apoptosis
cardiomyocyte surface area
and IGF-1R
GNAI1 and PLCG1 expression were decreased in the model +pcDNA-FLI-1+Klotho siRNA group compared with the model +pcDNA-FLI-1+NC siRNA group.
Conclusion
2
FLI-1 can inhibit IGF-1R/Gi/PLC pathway and reduce myocardial apoptosis and myocardial hypertrophy by up-regulating Klotho.
OLDFIELD C J, DUHAMEL T A, DHALLA N S. Mechanisms for the transition from physiological to pathological cardiac hypertrophy[J]. Can J Physiol Pharmacol, 2020, 98(2): 74-84. DOI: 10.1139/cjpp-2019-0566.
LIU B Y, LI L, LIU G L, et al . Baicalein attenuates cardiac hypertrophy in mice via suppressing oxidative stress and activating autophagy in cardiomyocytes[J ] . Acta Pharmacol Sin, 2021, 4 2(5): 701-714. DOI: 10.1038/s41401-020-0496-1..
WAN M X, YIN K K, YUAN J, et al . YQFM alleviated cardiac hypertrophy by apoptosis inhibition and autophagy regulation via PI3K/AKT/mTOR pathway[J ] . J Ethnopharmacol, 2022, 285: 114835. DOI: 10.1016/j.jep.2021.114835..
WANG Y F, HUANG Z, SUN M Y, et al . ETS transcription factors: Multifaceted players from cancer progression to tumor immunity[J ] . Biochim Biophys Acta Rev Cancer, 2023, 1878(3): 188872. DOI: 10.1016/j.bbcan.2023.188872.
BEN-DAVID Y, GAJENDRAN B, SAMPLE K M, et al . Current insights into the role of Fli-1 in hematopoiesis and malignant transformation[J ] . Cell Mol Life Sci, 2022, 79(3): 163-171. DOI: 10.1007/s00018-022-04160-1.
HALLER S T, KENNEDY D J, SHIDYAK A, et al . Monoclonal antibody against marinobufagenin reverses cardiac fibrosis in rats with chronic renal failure[J ] . Am J Hypertens, 2012, 25(6): 690-696. DOI: 10.1038/ajh.2012.17.
XIE B, HU F, LI M, et al . FLI-1 mediates tumor suppressor function via Klotho signaling in regulating CRC[J ] . Cell Bio l Int, 2020, 44(7): 1514-1522. DOI: 10.1002/cbin.11347..
PRUD'HOMME G J, KURT M, WANG Q H. Pathobiology of the klotho antiaging protein and therapeutic considerations[J]. Front Aging, 2022, 3: 931331. DOI: 10.3389/fragi.2022.931331.
CHEN K, WANG S, SUN Q W, et al . Klotho deficiency causes heart aging via impairing the Nrf2-GR pathway[J ] . Circ Res, 2021, 128(4): 492-507. DOI: 10.1161/CIRCRESAHA.120.317348..
李宝善, 马厚勋, 王艳娇, 等. Klotho基因转导延缓自发性高血压大鼠高血压进程及改善其心脏损害的作用研究[J]. 中华医学遗传学杂志, 2012, 29(6): 662-668. DOI: 10.3760/cma.j.issn.1003-9406.2012.06.008.
LI B S, MA H X, WANG Y J, et al . Klotho gene attenuates the progression of hypertension and heart damage in spontaneous hypertensive rats[J ] . Chin J Med Genet, 2012, 29(6): 662-668. DOI: 10.3760/cma.j.issn.1003-9406.2012.06.008.
邱雨美, 尹史帝, 董伟, 等. 薯蓣皂苷对异丙肾上腺素诱导H9c2心肌细胞肥大的保护作用[J]. 中药药理与临床, 2022, 38(2): 94-99. DOI: 10.13401/j.cnki.jsumc.2021.02.001.
QIU Y M, YIN S D, DONG W, et al . Protective effect of dioscin on isoproterenol-induced hypertrophy of H9c2 cardiomyocytes[J ] . Pharmacol Clin Chin Mater Med, 2022, 38(2): 94-99. DOI: 10.13401/j.cnki.jsumc.2021.02.001.
REN Z N, YU P, LI D D, et al . Single-cell reconstruction of progression trajectory reveals intervention principles in pathological cardiac hypertrophy[J ] . Circulation, 2020, 141(21): 1704-1719. DOI: 10.1161/CIRCULATIONAHA.119.043053.
PROTSENKO Y L, BALAKIN A A, KUZNETSOV D A, et al . Contractility of right ventricular myocardium in male and female rats during physiological and pathological hypertrophy[J ] . Bull Exp Biol Med, 2017, 162(3): 303-305. DOI: 10.1007/s10517-017-3600-x.
SUN T L, LI W Q, TONG X L, et al . Xanthohumol attenuates isoprenaline-induced cardiac hypertrophy and fibrosis through regulating PTEN/AKT/mTOR pathway[J ] . Eur J Pharmacol, 2021, 891: 173690. DOI: 10.1016/j.ejphar.2020.173690.
TANAKA M, YAMAGUCHI S, YAMAZAKI Y, et al . Somatic chromosomal translocation between Ewsr1 and Fli1 loci leads to dilated cardiomyopathy in a mouse model[J ] . Sci Rep, 2015, 5: 7826. DOI: 10.1038/srep07826.
CHENG Y, SHEN A L, WU X Y, et al . Qingda Granule attenuates angiotensin Ⅱ-induced cardiac hypertrophy and apoptosis and modulates the PI3K/AKT pathwa y[J ] . Biomedecine Pharmacother, 2021, 133: 111022. DOI: 10.1016/j.biopha.2020.111022.
BRUCKHEIMER E M, CHO S H, SARKISS M, et al . The Bcl-2 gene family and apoptosis[M ] // AL-RUBEAI M. Apoptosis. Berlin, Heidelberg: Springer Berlin Heidelberg, 1998: 75-105. DOI: 10.1007/bfb0102306.
FAN T J, HAN L H, CONG R S, et al . Caspase family proteases and apoptosis[J ] . Acta Biochim Biophys Sin (Shanghai), 2005, 37(11): 719-727. DOI: 10.1111/j.1745-7270.2005.00108.x.
DING J Q, TANG Q, LUO B H, et al . Klotho inhibits angiotensin Ⅱ-induced cardiac hypertrophy, fibrosis, and dysfunction in mice through suppression of transforming growth factor-β1 signaling pathway[J ] . Eur J Pharmacol, 2019, 859: 172549. DOI: 10.1016/j.ejphar.2019.172549.
XIE J, CHA S K, AN S W, et al . Cardioprotection by Klotho through downregulation of TRPC6 channels in the mouse heart[J ] . Nat Commun, 2012, 3: 1238. DOI: 10.1038/ncomms2240.
ZHOU X X, FANG X S, JIANG Y J, et al . Klotho, an anti-aging gene, acts as a tumor suppressor and inhibitor of IGF-1R signaling in diffuse larg e B cell lymphoma[J ] . J Hematol Oncol, 2017, 10(1): 37. DOI: 10.1186/s13045-017-0391-5.
OCK S, HAM W, KANG C W, et al . IGF-1 protects against angiotensin Ⅱ-induced cardiac fibrosis by targeting αSMA[J ] . Cell Death Dis, 2021, 12(7): 688. DOI: 10.1038/s41419-021-03965-5.
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621