Page 49 - 南京医科大学自然版
P. 49
第44卷第11期 潘锦堃,李超普,张 许,等. miR⁃199a⁃5p在肝脏组织中的表达及其作用的初步研究[J].
2024年11月 南京医科大学学报(自然科学版),2024,44(11):1510-1516 ·1515 ·
A B C
NC⁃mimic NC⁃mimic miR⁃199a⁃5p⁃mimic NC⁃mimic
miR⁃199a⁃5p⁃mimic CD36 100 kDa 1.5 miR⁃199a⁃5p⁃mimic
1.5
Relative mRNA level 1.0 Tubulin 180 kDa Protein expression/Calnexin 1.0
*
FAS
45 kDa
ATGL
0.5
0.5
60 kDa
0 0
SREBP1⁃C ACC FAS CD36 ATGL HSL CPTA⁃α CD36 FAS ATGL
A:The expression levels of lipid metabolism⁃related genes in Hepa1⁃6 cells after overexpression of miR⁃199a⁃5p were detected by RT⁃qPCR. B:
The protein levels of CD36,FAS and ATGL in Hepa1⁃6 cells after overexpression of miR⁃199a⁃5p were detected by Western blot. C:Grayscale analysis
*
of protein immunoblotting. P < 0.05(n=3).
图4 miR⁃199a⁃5p降低Hepa1⁃6细胞中CD36的蛋白表达
Figure 4 miR⁃199a⁃5p decreased protein levels of CD36 in Hepa1⁃6 cells
要作用 [33] 。 ing the global public health agenda for NAFLD:a consen⁃
本研究发现,在 ob/ob 小鼠肝脏 miRNA 数据库 sus statement[J]. Nat Rev Gastroenterol Hepatol,2022,
GEO13840中,miR⁃199a⁃5p在ob/ob小鼠肝脏中表达 19(1):60-78
水平增加,提示该miRNA可能在肝脏能量代谢中发 [5] ZHOU J H,ZHOU F,WANG W X,et al. Epidemiological
features of NAFLD from 1999 to 2018 in China[J]. Hepa⁃
挥重要作用。此外,在高脂饮食和饥饿状态下,小
tology,2020,71(5):1851-1864
鼠肝脏中 miR⁃199a⁃5p 的表达水平显著增加,提示
[6] WATT M J,MIOTTO P M,DE NARDO W,et al. The liv⁃
在肝脏脂质积累的过程中miR⁃199a⁃5p表达水平增
er as an endocrine organ⁃linking NAFLD and insulin re⁃
加。进一步研究表明,过表达 miR⁃199a⁃5p 能够降 sistance[J]. Endocr Rev,2019,40(5):1367-1393
低肝细胞内 TAG 含量,而抑制 miR⁃199a⁃5p 会增加 [7] GRABNER G F,XIE H,SCHWEIGER M,et al. Lipoly⁃
肝细胞内 TAG 含量,提示 miR⁃199a⁃5p 可能参与调 sis:cellular mechanisms for lipid mobilization from fat
控肝细胞内脂质水平。miRDB 的预测和双荧光素 stores[J]. Nat Metab,2021,3(11):1445-1465
酶报告基因的实验结果显示,miR⁃199a⁃5p 靶向 [8] LA SALA L,CARLINI V,CONTE C,et al. Metabolic dis⁃
CD36 mRNA 的 3′ UTR 区域抑制其翻译,降低其蛋 orders affecting the liver and heart:therapeutic efficacy of
miRNA⁃based therapies?[J]. Pharmacol Res,2024,201:
白水平。共转染过表达miR⁃199a⁃5p和CD36后,肝
107083
细胞内 TAG 含量差异无统计学意义,说明过表达
[9] SHANG R,LEE S,SENAVIRATHNE G,et al. microR⁃
CD36 可以抵消 miR⁃199a⁃5p 引起的细胞内 TAG 含
NAs in action:biogenesis,function and regulation[J].
量降低。这证实了 miR⁃199a⁃5p 通过靶向 CD36 来
Nat Rev Genet,2023,24(12):816-833
调节肝细胞对脂肪酸的摄取。 [10]DELUCAS M,SANCHEZ J,PALOU A,et al. The impact
本研究结果表明,在肝脏脂质积累过程中,miR⁃ of diet on miRNA regulation and its implications for health:
199a⁃5p的表达水平增加。miR⁃199a⁃5p表达的增加 a systematic review[J]. Nutrients,2024,16(6):770
抑制了 CD36 蛋白的表达,降低了肝细胞内 TAG 含 [11]GUTBROD M J,MARTIENSSEN R A. Conserved chromo⁃
量,有助于改善肝细胞内的脂质稳态。 somal functions of RNA interference[J]. Nat Rev Genet,
2020,21(5):311-331
[参考文献]
[12]MEDLEY J C,PANZADE G,ZINOVYEVA A Y. MicroRNA
[1] HORN P,TACKE F. Metabolic reprogramming in liver fi⁃ strand selection:unwinding the rules[J]. Wiley Interdis⁃
brosis[J]. Cell Metab,2024,36(7):1439-1455 cip Rev RNA,2021,12(3):e1627
[2] TREFTS E,GANNON M,WASSERMAN D H. The liver[J]. [13]CUI Y,QI Y,DING L,et al. miRNA dosage control in de⁃
Curr Biol,2017,27(21):1147-1151 velopment and human disease[J]. Trends Cell Biol,
[3] 周子欣,杨旭乐,张 许,等. 去泛素化酶YOD1调控肝 2024,34(1):31-47
脏脂代谢的初步研究[J]. 南京医科大学学报(自然科 [14]ZHANG C,WANG P,LI Y Q,et al. Role of microRNAs
学版),2021,41(12):1735-1740 in the development of hepatocellular carcinoma in nonal⁃
[4] LAZARUS J V,MARK H E,ANSTEE Q M,et al. Advanc⁃ coholic fatty liver disease[J]. Anat Rec,2019,302(2):