Exploring the Relative Differential Protein Expression of Carbon Tetrachloride-induced Acute Liver Injury in Mice Based on the Proteomics Method

doi:10.13560/j.cnki.biotech.bull.1985.2024-0090

Abstract

Abstract:

Objective Labker quantitative (TMT) proteomics was used to explore the mechanism of chemical inducer (carbon tetrachloride, CCl₄) causing acute liver injury in mice. Method Twenty SPF male BALB/C mice were randomly divided into control and induction groups, with 10 mice in each group, induced by intraperitoneal injection for 8 weeks (2 times/week). The degree of liver injury was evaluated by measuring the blood biochemical level and liver histopathological sections. Proteomic analysis was performed by tandem mass spectrometry labeling technology (TMT), including gene Ontology (GO) annotation, KEGG pathways, and protein interaction network analysis of the found differential proteins. Result Compared with the control group, blood indicator of aspartate aminotransferase (AST) was significantly higher (P<0.05); alanine aminotransferase (ALT), y-glutamyl transpeptadase (GGT), total biliary acid (TBA) (P<0.01). Moreover, liver histopathological sections showed significant liver injury in the CCl₄ induction group. A total of 5 955 proteins were identified using TMT, with 440 increased intensity and 294 decreased, and differential proteins played important roles in protein expression difference, biomarker application and participation in classical signaling pathways (JAK-STAT, PI3K-Akt, Rap 1, GnRH, AGE-RAGE). There was a significant enrichment of differential proteins in classical signaling pathways and a relatively high enrichment. Conclusion CCl₄ as an ideal chemical inducer for liver injury evaluation, it is involved in several key processes such as immunity, cell division, apoptosis and autophagy, inflammation and tumor formation. It reduces the pathological mechanism of liver injury in multiple directions and targets and provides a solid theoretical basis and perspective for the research and development of liver protection drugs.

Key words: proteomics, carbon tetrachloride, liver injury, mice

LI Wei-hua, WU Jing, JIN Xue-qin, LEI Yan-li. Exploring the Relative Differential Protein Expression of Carbon Tetrachloride-induced Acute Liver Injury in Mice Based on the Proteomics Method[J]. Biotechnology Bulletin, 2025, 41(2): 331-342.

Figures/Tables 7

References 35

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调节（上调/下调） Regulation（Up/Down）	蛋白编号Accession	功能描述 Description	基因符号Gene symbol	分子量Mw/kD	比值（CCl₄/Control） Ratio（CCl₄/Control）	P值 P-value
Up	P50236	Bile salt sulfotransferase 2	Sult2a2	33.3	13.086	1.71E-04
	Q64449	C-type mannose receptor 2	Mrc2	167	5.077	3.11E-04
	P13745	Glutathione S-transferase A1	Gsta1	25.6	4.575	2.36E-03
	Q9R100	Cadherin-17	Cdh17	91.6	3.976	2.38E-04
	P97501	Dimethylaniline monooxygenase ［N-oxide-forming］ 3	Fmo3	60.5	3.438	1.25E-03
	Q6IS41	Solute carrier family 25 member 47	Slc25a47	33.6	3.224	2.49E-02
	Q9CZS1	Aldehyde dehydrogenase X， mitochondrial	Aldh1b1	57.5	3.108	1.66E-05
	Q8BG95	Protein phosphatase 1 regulatory subunit 12B	Ppp1r12b	109	3.007	1.19E-02
Down	Q9QXS8	Probable N-acetyltransferase CML5	Cml5	25.7	0.089	2.98E-03
	Q61694	NADPH-dependent 3-keto-steroid reductase Hsd3b5	Hsd3b5	41.9	0.167	1.24E-03
	Q63836	Selenium-binding protein 2	Selenbp2	52.6	0.156	4.23E-04
	Q60991	Cytochrome P450 7B1	Cyp7b1	58.4	0.169	1.52E-04
	Q9Z0N2	Eukaryotic translation initiation factor 2 subunit 3， Y-linked	Eif2s3y	51.1	0.21	6.87E-05
	O35728	Cytochrome P450 4A14	Cyp4a14	58.7	0.221	1.30E-03
	Q9QXZ6	Solute carrier organic anion transporter family member 1A1	Slco1a1	74.3	0.25	3.72E-04
	Q61646	Haptoglobin	Hp	38.7	0.354	1.78E-02
	P46425	Glutathione S-transferase P 2	Gstp2	23.5	0.393	1.37E-03
	Q3UP75	UDP-glucuronosyltransferase 3A1	Ugt3a1	59.7	0.394	5.09E-04

调节（上调/下调） Regulation（Up/Down）	蛋白编号Accession	功能描述 Description	基因符号Gene symbol	分子量Mw/kD	比值（CCl₄/Control） Ratio（CCl₄/Control）	P值 P-value
Up	P50236	Bile salt sulfotransferase 2	Sult2a2	33.3	13.086	1.71E-04
	Q64449	C-type mannose receptor 2	Mrc2	167	5.077	3.11E-04
	P13745	Glutathione S-transferase A1	Gsta1	25.6	4.575	2.36E-03
	Q9R100	Cadherin-17	Cdh17	91.6	3.976	2.38E-04
	P97501	Dimethylaniline monooxygenase ［N-oxide-forming］ 3	Fmo3	60.5	3.438	1.25E-03
	Q6IS41	Solute carrier family 25 member 47	Slc25a47	33.6	3.224	2.49E-02
	Q9CZS1	Aldehyde dehydrogenase X， mitochondrial	Aldh1b1	57.5	3.108	1.66E-05
	Q8BG95	Protein phosphatase 1 regulatory subunit 12B	Ppp1r12b	109	3.007	1.19E-02
Down	Q9QXS8	Probable N-acetyltransferase CML5	Cml5	25.7	0.089	2.98E-03
	Q61694	NADPH-dependent 3-keto-steroid reductase Hsd3b5	Hsd3b5	41.9	0.167	1.24E-03
	Q63836	Selenium-binding protein 2	Selenbp2	52.6	0.156	4.23E-04
	Q60991	Cytochrome P450 7B1	Cyp7b1	58.4	0.169	1.52E-04
	Q9Z0N2	Eukaryotic translation initiation factor 2 subunit 3， Y-linked	Eif2s3y	51.1	0.21	6.87E-05
	O35728	Cytochrome P450 4A14	Cyp4a14	58.7	0.221	1.30E-03
	Q9QXZ6	Solute carrier organic anion transporter family member 1A1	Slco1a1	74.3	0.25	3.72E-04
	Q61646	Haptoglobin	Hp	38.7	0.354	1.78E-02
	P46425	Glutathione S-transferase P 2	Gstp2	23.5	0.393	1.37E-03
	Q3UP75	UDP-glucuronosyltransferase 3A1	Ugt3a1	59.7	0.394	5.09E-04

疾病 Diseases	相关的蛋白 Related proteins	调节（上调/下调） Regulation（Up/Down）	费希尔精确检验P值Fisher's exact test P value
Proteoglycans in cancer	P05480 Q63844 P51885 P20444 P49710 Q8BG95 P28654 P70336 P49817 P15379 Q01149 Q8BTM8 P70227 P26041 Q9JKF1 P26040 P11276 P11087	Up	7.58E-04
Fluid shear stress and atherosclerosis	Q64337 P05480 P70236 P10648 P16460 Q09014 Q05144 Q64669 P61957 Q5EG47 P49817 Q99L20 P13745 Q60875	Up	1.45E-03
Hypertrophic cardiomyopathy	Q6IRU2 P58771 Q60675 P82347 O54950 Q5EG47 A2ARA8 P31001 P09470	Up	1.53E-03
MicroRNAs in cancer	P20152 P54227 Q63844 P58771 P63280 P20444 D3Z7P3 P21447 Q64261 P15379 P26645 P26040	Up	4.36E-03
Tuberculosis	P05480 Q64449 Q63844 P04441 P19973 Q07813 P51437 O70370 P18242 P11835 O89053 P05555 P08508	Up	6.42E-03
Leishmaniasis	Q63844 P28667 Q09014 P11835 Q61093 P05555 P08508	Up	5.11E-03
Type II diabetes mellitus	Q63844 P52480 Q91W97 O08528 P28867 P17710	Up	2.66E-03
C-type lectin receptor signaling pathway	Q9WVL2 P05480 Q63844 P19973 Q9WTK5 P28867 P70227	Up	3.56E-02
Coronavirus disease-COVID-19	P62918 O09167 P62852 P62849 P62267 P47915 P27659 P61514 P47964 P14115 P62754 P83882 Q9D8E6 P67984 P62830 P62281 Q9CPR4 Q6ZWV7 Q8BP67 P62301 P62751 P41105 P47963 Q9D823 Q9JJI8 P12970 P61255 P61358 Q6ZWV3 P47911 P84099 P62900 Q9D1R9 Q8K182 Q01279 Q8K0E8 Q8VCM7 Q8VCG4 E9PV24 P01029 Q8BH35 P62855	Down	1.72E-20
African trypanosomiasis	Q00623 P02088 P02089 P01942	Down	1.11E-02

疾病 Diseases	相关的蛋白 Related proteins	调节（上调/下调） Regulation（Up/Down）	费希尔精确检验P值Fisher's exact test P value
Proteoglycans in cancer	P05480 Q63844 P51885 P20444 P49710 Q8BG95 P28654 P70336 P49817 P15379 Q01149 Q8BTM8 P70227 P26041 Q9JKF1 P26040 P11276 P11087	Up	7.58E-04
Fluid shear stress and atherosclerosis	Q64337 P05480 P70236 P10648 P16460 Q09014 Q05144 Q64669 P61957 Q5EG47 P49817 Q99L20 P13745 Q60875	Up	1.45E-03
Hypertrophic cardiomyopathy	Q6IRU2 P58771 Q60675 P82347 O54950 Q5EG47 A2ARA8 P31001 P09470	Up	1.53E-03
MicroRNAs in cancer	P20152 P54227 Q63844 P58771 P63280 P20444 D3Z7P3 P21447 Q64261 P15379 P26645 P26040	Up	4.36E-03
Tuberculosis	P05480 Q64449 Q63844 P04441 P19973 Q07813 P51437 O70370 P18242 P11835 O89053 P05555 P08508	Up	6.42E-03
Leishmaniasis	Q63844 P28667 Q09014 P11835 Q61093 P05555 P08508	Up	5.11E-03
Type II diabetes mellitus	Q63844 P52480 Q91W97 O08528 P28867 P17710	Up	2.66E-03
C-type lectin receptor signaling pathway	Q9WVL2 P05480 Q63844 P19973 Q9WTK5 P28867 P70227	Up	3.56E-02
Coronavirus disease-COVID-19	P62918 O09167 P62852 P62849 P62267 P47915 P27659 P61514 P47964 P14115 P62754 P83882 Q9D8E6 P67984 P62830 P62281 Q9CPR4 Q6ZWV7 Q8BP67 P62301 P62751 P41105 P47963 Q9D823 Q9JJI8 P12970 P61255 P61358 Q6ZWV3 P47911 P84099 P62900 Q9D1R9 Q8K182 Q01279 Q8K0E8 Q8VCM7 Q8VCG4 E9PV24 P01029 Q8BH35 P62855	Down	1.72E-20
African trypanosomiasis	Q00623 P02088 P02089 P01942	Down	1.11E-02

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