Regulatory effect of microRNA-544 on liver injury in mice with sepsis and its mechanism

Songmei GUAN; Peiwu HUANG; Xiaobao GONG; Kangqiang LIN; Shigang DUAN

doi:10.12449/JCH250922

Volume 41 Issue 9

Sep. 2025

Turn off MathJax

Article Contents

Article Navigation > Journal of Clinical Hepatology > 2025 > 41(9): 1861-1867

PDF( 4734 KB)

Regulatory effect of microRNA-544 on liver injury in mice with sepsis and its mechanism

DOI: 10.12449/JCH250922

1.
Department of Pharmacy The Second Affiliated Hospital of GuangdongMedical University Zhanjiang Guangdong 524000 China
2.
Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated Hospital of Guangdong Medical University Zhanjiang Guangdong 524000 China
3.
The First Clinical College of Guangdong Medical University，Zhanjiang，Guangdong 524000，China
4.
Department of Pharmacy，Chongqing University Cancer Hospital，Chongqing 400700，China

Research funding:

Zhanjiang Science and Technology Development Special Projects (2021A05101);

Zhanjiang Science and Technology Development Special Projects (2022A01147);

High-level Talent Start-up Project of the Second Affiliated Hospital of Guangdong Medical University (21H03);

High-level Talent Start-up Project of the Second Affiliated Hospital of Guangdong Medical University (23H02)

More Information

Corresponding author: LIN Kangqiang， lkq1008@foxmail.com （ORCID： 0000-0002-6313-8336）; DUAN Shigang， 980233908@qq.com （ORCID： 0000-0002-4786-1612）
Received Date: 2025-01-22
Accepted Date: 2025-06-06
Published Date: 2025-09-25

Abstract

Abstract

Objective To investigate the role and potential mechanism of microRNA-544 （miRNA-544） in lipopolysaccharide （LPS）-induced liver injury in mice with sepsis， and to provide a new target for the treatment of liver injury in sepsis. Methods A total of 40 C57BL/6J mice were randomly divided into control group （intraperitoneal injection of normal saline）， model group （intraperitoneal injection of LPS at a dose of 5 mg/kg）， agonist group （intraperitoneal injection of LPS and miR-544 agonist at a dose of 5 mg/kg）， and miR-544 inhibitor group （intraperitoneal injection of LPS and miR-544 inhibitor at a dose of 5 mg/kg）， with 10 mice in each group. An automatic biochemical analyzer was used to measure the levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and total bilirubin （TBil） in serum and the liver； Western blot was used to measure the expression levels of monocyte chemotactic protein-1 （MCP-1）， CD16/32， and proteins associated with the NF-κB signaling pathway in the liver； q-PCR and ELISA were used to measure the expression levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in serum. A one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. Results Compared with the control group， the model group of LPS-induced sepsis had a significant reduction in the expression level of miR-544 in serum and liver tissue （P<0.01）， significant pathological changes of the liver （such as inflammatory cell infiltration and central vein congestion）， and significant increases in the levels of liver injury markers （ALT， AST， and TBil） in serum and the liver （all P<0.001）， the expression levels of inflammatory factors （MCP-1， CD16/32， TNF-α， IL-6， and IL-1β）（all P<0.01）， and the phosphorylation levels of key proteins of the NF-κB pathway （p-IKK， p-I-NF-κ， and p-p65）（all P<0.01）. Compared with the model group， the miR-544 inhibitor group had a significant reduction in the expression level of miR-544 in serum and liver tissue （P<0.01）， aggravated pathological changes of the liver， and significant increases in the levels of liver injury markers and inflammatory factors （ALT， AST， TBil， MCP-1， CD16/32， TNF-α， IL-6， and IL-1）（all P<0.05）， as well as significant increases in the phosphorylation levels of key proteins of the NF-κB pathway （p-IKK， p-I-κB-α， and p-p65）（all P<0.01）. On the contrary， the miR-544 agonist group had a significant increase in the expression level of miR-544 in serum and liver tissue （P<0.01）， significant alleviation of liver pathological changes， and significant reductions in the levels of liver injury markers and inflammatory factors （ALT， AST， TBil， MCP-1， CD16/32， TNF-α， IL-6， and IL-1β）（all P<0.05）， as well as significant reductions in the phosphorylation levels of key proteins of the NF-κB pathway （p-IKK， p-I-κB-α， and p-p65）（all P<0.05）. Conclusion This study shows that miR-544 can alleviate LPS-induced liver injury in mice with sepsis by inhibiting the expression of inflammatory-related proteins and the activation of the NF-κB signaling pathway.
- Sepsis,
- Lipopolysaccharides,
- MicroRNAs,
- Mice， Inbred C57BL

FullText(HTML)

References(27)

References

[1]	CAO LP, LI ZH, YANG ZZ, et al. Ferulic acid positively modulates the inflammatory response to septic liver injury through the GSK-3β/NF-κB/CREB pathway[J]. Life Sci, 2021, 277: 119584. DOI: 10.1016/j.lfs.2021.119584.
[2]	ABDELNASER M, ALAAELDIN R, ATTYA ME, et al. Hepatoprotective potential of gabapentin in cecal ligation and puncture-induced sepsis; targeting oxidative stress, apoptosis, and NF-κB/MAPK signaling pathways[J]. Life Sci, 2023, 320: 121562. DOI: 10.1016/j.lfs.2023.121562.
[3]	HAO CP, LI QH, ZHANG CC, et al. Analysis of the current status and influencing factors of quality of life of sepsis survivors in intensive care units[J]. Chin J Crit Care Med, 2024, 36( 1): 23- 27. DOI: 10.3760/cma.j.issn.2095-4350.2024.01.004. 郝翠平, 李秋华, 张翠翠, 等. 重症监护病房脓毒症存活者生活质量现状及其影响因素分析[J]. 中华危重病急救医学, 2024, 36( 1): 23- 27. DOI: 10.3760/cma.j.issn.2095-4350.2024.01.004.
[4]	XU DZ, ZHANG SX, WANG K, et al. Value of the serum levels of Clusterin and sphingosine 1-phosphate in assessing the prognosis of sepsis patients with acute liver injury[J]. J Clin Hepatol, 2023, 39( 12): 2867- 2872. DOI: 10.3969/j.issn.1001-5256.2023.12.018. 徐大洲, 张树贤, 王坤, 等. 血清簇集蛋白、1-磷酸鞘氨醇水平对脓毒症急性肝损伤患者的预后价值[J]. 临床肝胆病杂志, 2023, 39( 12): 2867- 2872. DOI: 10.3969/j.issn.1001-5256.2023.12.018.
[5]	HERRÁN-MONGE R, MURIEL-BOMBÍN A, GARCÍA-GARCÍA MM, et al. Epidemiology and changes in mortality of sepsis after the implementation of surviving sepsis campaign guidelines[J]. J Intensive Care Med, 2019, 34( 9): 740- 750. DOI: 10.1177/0885066617711882.
[6]	BIEBELBERG B, RHEE C, CHEN T, et al. Heterogeneity of sepsis presentations and mortality rates[J]. Ann Intern Med, 2024, 177( 7): 985- 987. DOI: 10.7326/M24-0400.
[7]	CHEN LF, LU Q, DENG FM, et al. miR-103a-3p could attenuate sepsis-induced liver injury by targeting HMGB1[J]. Inflammation, 2020, 43( 6): 2075- 2086. DOI: 10.1007/s10753-020-01275-0.
[8]	MITRA R, ADAMS CM, JIANG W, et al. Pan-cancer analysis reveals cooperativity of both strands of microRNA that regulate tumorigenesis and patient survival[J]. Nat Commun, 2020, 11( 1): 968. DOI: 10.1038/s41467-020-14713-2.
[9]	SZILÁGYI B, FEJES Z, PÓLISKA S, et al. Reduced miR-26b expression in megakaryocytes and platelets contributes to elevated level of platelet activation status in sepsis[J]. Int J Mol Sci, 2020, 21( 3): 866. DOI: 10.3390/ijms21030866.
[10]	CHEN WW, MA XY, ZHANG P, et al. miR-212-3p inhibits LPS-induced inflammatory response through targeting HMGB1 in murine macrophages[J]. Exp Cell Res, 2017, 350( 2): 318- 326. DOI: 10.1016/j.yexcr.2016.12.008.
[11]	WANG P, ZHANG X, LI FL, et al. miR-130b attenuates vascular inflammation via negatively regulating tumor progression locus 2(Tpl2) expression[J]. Int Immunopharmacol, 2017, 51: 9- 16. DOI: 10.1016/j.intimp.2017.07.020.
[12]	ROY SG. Regulation of autophagy by miRNAs in human diseases[J]. Nucleus(Calcutta), 2021, 64( 3): 317- 329. DOI: 10.1007/s13237-021-00378-9.
[13]	SONG WC, MU HL, WU J, et al. miR-544 regulates dairy goat male germline stem cell self-renewal via targeting PLZF[J]. J Cell Biochem, 2015, 116( 10): 2155- 2165. DOI: 10.1002/jcb.25172.
[14]	MO XM, LI HH, LIU M, et al. Downregulation of GSK3β by miR-544a to maintain self-renewal ability of lung caner stem cells[J]. Oncol Lett, 2014, 8( 4): 1731- 1734. DOI: 10.3892/ol.2014.2387.
[15]	SUN T, LIU Y, LIU LY, et al. microRNA-544 attenuates diabetic renal injury via suppressing glomerulosclerosis and inflammation by targeting FASN[J]. Gene, 2020, 723: 143986. DOI: 10.1016/j.gene.2019.143986.
[16]	LI CG, LI X, ZHAO BC, et al. Exosomes derived from miR-544-modified mesenchymal stem cells promote recovery after spinal cord injury[J]. Arch Physiol Biochem, 2020, 126( 4): 369- 375. DOI: 10.1080/13813455.2019.1691601.
[17]	GRONDMAN I, PIRVU A, RIZA A, et al. Biomarkers of inflammation and the etiology of sepsis[J]. Biochem Soc Trans, 2020, 48( 1): 1- 14. DOI: 10.1042/BST20190029.
[18]	DONG XJ, LIU QX, ZHENG Q, et al. Alterations of B cells in immunosuppressive phase of septic shock patients[J]. Crit Care Med, 2020, 48( 6): 815- 821. DOI: 10.1097/CCM.0000000000004309.
[19]	LI H, CHEN Q, HAN XD. The role and mechanism of liver in the occurrence and development of sepsis[J]. Med J Commun, 2020, 34( 1): 11- 14. DOI: 10.19767/j.cnki.32-1412.2020.01.004. 李晗, 陈强, 韩旭东. 肝脏在脓毒症发生发展中的作用及机制[J]. 交通医学, 2020, 34( 1): 11- 14. DOI: 10.19767/j.cnki.32-1412.2020.01.004.
[20]	LONG SR, LIU RD, KUMAR DV, et al. Immune protection of a helminth protein in the DSS-induced colitis model in mice[J]. Front Immunol, 2021, 12: 664998. DOI: 10.3389/fimmu.2021.664998.
[21]	WU YJ, WANG QH, LI M, et al. SLAMF7 regulates the inflammatory response in macrophages during polymicrobial sepsis[J]. J Clin Invest, 2023, 133( 6): e150224. DOI: 10.1172/JCI150224.
[22]	LIU D, HUANG SY, SUN JH, et al. Sepsis-induced immunosuppression: Mechanisms, diagnosis and current treatment options[J]. Mil Med Res, 2022, 9( 1): 56. DOI: 10.1186/s40779-022-00422-y.
[23]	TONG X, TIAN L, XU JF, et al. Effect of Jinzhi on the expression of serum inflammatory factors in sepsis mice[J]. J Emerg Tradit Chin Med, 2023, 32( 6): 954- 957. DOI: 10.3969/j.issn.1004-745X.2023.06.004. 童昕, 田良, 许建峰, 等. 金汁对脓毒症小鼠血清炎症因子表达的影响[J]. 中国中医急症, 2023, 32( 6): 954- 957. DOI: 10.3969/j.issn.1004-745X.2023.06.004.
[24]	DAS UN. Infection, inflammation, and immunity in sepsis[J]. Biomolecules, 2023, 13( 9): 1332. DOI: 10.3390/biom13091332.
[25]	CHEN XS, WANG SH, LIU CY, et al. Losartan attenuates sepsis-induced cardiomyopathy by regulating macrophage polarization via TLR4-mediated NF-κB and MAPK signaling[J]. Pharmacol Res, 2022, 185: 106473. DOI: 10.1016/j.phrs.2022.106473.
[26]	JIA XH, LI XL, DONG FX, et al. Palmatine ameliorates CLP-induced sepsis via inhibition of NF-κB signaling pathway[J]. Cent South Pharm, 2023, 21( 3): 557- 561. DOI: 10.7539/j.issn.1672-2981.2023.03.001. 贾鑫航, 李晓玲, 董方昕, 等. 巴马汀通过抑制NF-κB信号通路改善CLP诱导的脓毒症[J]. 中南药学, 2023, 21( 3): 557- 561. DOI: 10.7539/j.issn.1672-2981.2023.03.001.
[27]	GONG XB, YANG Y, HUANG LG, et al. Antioxidation, anti-inflammation and anti-apoptosis by paeonol in LPS/d-GalN-induced acute liver failure in mice[J]. Int Immunopharmacol, 2017, 46: 124- 132. DOI: 10.1016/j.intimp.2017.03.003.

Relative Articles

Supplements(0)

Cited By

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(5) / Tables(1)

Get Citation

PDF

XML

Article Metrics

Article views (124) PDF downloads(9)

Regulatory effect of microRNA-544 on liver injury in mice with sepsis and its mechanism

DOI: 10.12449/JCH250922

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Regulatory effect of microRNA-544 on liver injury in mice with sepsis and its mechanism

DOI: 10.12449/JCH250922

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

About Journal

Submission Guideline

Journal Online

Hepatobiliary College

Guidelines

Export File

Citation

Format

Content