Hepatoma-derived growth factor participates in concanavalin A-induced hepatitis

被引：8

作者：

Wang, E-Ming ^{[1
,2
]}

Hu, Tsung-Hui ^{[3
]}

Huang, Chao-Cheng ^{[4
,5
,6
]}

Chang, Yi-Chen ^{[7
,8
]}

Yang, Shih-Ming ^{[9
]}

Huang, Shih-Tsung ^{[7
,8
,10
]}

Wu, Jian-Ching ^{[4
,5
,6
]}

Ma, Yi-Ling ^{[11
]}

Chan, Hoi-Hung ^{[12
]}

Liu, Li-Feng ^{[13
]}

Lu, Wen-Bin ^{[9
]}

Kung, Mei-Lang ^{[14
]}

Wen, Zhi-Hong ^{[15
]}

Wang, Jui-Chu ^{[5
,6
]}

Ko, Chou-Yuan ^{[16
]}

Tsai, Wei-Lun ^{[2
]}

Chu, Tian-Huei ^{[4
,17
]}

Tai, Ming-Hong ^{[1
,7
,8
,9
,18
,19
]}

机构：

[1] Natl Sun Yat Sen Univ, Dept Biol Sci, Kaohsiung, Taiwan

[2] Kaohsiung Vet Gen Hosp, Div Gastroenterol & Hepatol, Dept Internal Med, Kaohsiung, Taiwan

[3] Chang Gung Univ, Coll Med, Kaohsiung Chang Gung Mem Hosp, Div Hepatogastroenterol,Dept Internal Med, Kaohsiung, Taiwan

[4] Kaohsiung Chang Gung Mem Hosp, Biobank & Tissue Bank, Kaohsiung, Taiwan

[5] Kaohsiung Chang Gung Mem Hosp, Dept Pathol, Kaohsiung, Taiwan

[6] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan

[7] Natl Sun Yat Sen Univ, Doctoral Degree Program Marine Biotechnol, Kaohsiung, Taiwan

[8] Acad Sinica, Kaohsiung, Taiwan

[9] Natl Sun Yat Sen Univ, Inst Biomed Sci, 70 Lien Hai Rd, Kaohsiung 80424, Taiwan

[10] LabTurbo Biotech Corp, Taipei, Taiwan

[11] Kaohsiung Vet Gen Hosp, Div Nephrol, Kaohsiung, Taiwan

[12] Conde S Januario Hosp, Dept Med, Div Gastroenterol, Macau, Peoples R China

[13] I Shou Univ, Dept Biol Sci & Technol, Kaohsiung, Taiwan

[14] Kaohsiung Vet Gen Hosp, Dept Med Educ & Res, Kaohsiung, Taiwan

[15] Natl Sun Yat Sen Univ, Asia Pacific Ocean Res Ctr, Dept Marine Biotechnol & Resources, Kaohsiung, Taiwan

[16] Kaohsiung Armed Forces Gen Hosp, Dept Gastroenterol, Kaohsiung, Taiwan

[17] Kaohsiung Chang Gung Mem Hosp, Dept Med Res, 123 Ta Pei Rd, Kaohsiung 83301, Taiwan

[18] Natl Sun Yat Sen Univ, Ctr Neurosci, Kaohsiung, Taiwan

[19] Kaohsiung Med Univ, Regenerat Med & Cell Therapy Res Ctr, Kaohsiung, Taiwan

来源：

FASEB JOURNAL | 2020年 / 34卷 / 12期

关键词：

acute hepatitis; concanavalin A; hepatoma-derived growth factor; neutrophils; NECROSIS-FACTOR-ALPHA; NEUTROPHIL MIGRATION; FACTOR HDGF; TNF-ALPHA; LIVER; INFLAMMATION; CELLS; HEPATOCYTES; EXPRESSION; AUTOPHAGY;

D O I：

10.1096/fj.202000511RR

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Hepatitis is an important health problem worldwide. Novel molecular targets are in demand for detection and management of hepatitis. Hepatoma-derived growth factor (HDGF) has been delineated to participate in hepatic fibrosis and liver carcinogenesis. However, the relationship between hepatitis and HDGF remains unclear. This study aimed to elucidate the role of HDGF during hepatitis using concanavalin A (ConA)-induced hepatitis model. In cultured hepatocytes, ConA treatment-elicited HDGF upregulation at transcriptional level and promoted HDGF secretion while reducing intracellular HDGF protein level and cellular viability. Similarly, mice receiving ConA administration exhibited reduced hepatic HDGF expression and elevated circulating HDGF level, which was positively correlated with serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. By using HDGF knockout (KO) mice, it was found the ConA-evoked cell death was prominently alleviated in KO compared with control. Besides, it was delineated HDGF ablation conferred protection by suppressing the ConA-induced neutrophils recruitment in livers. Above all, the ConA-mediated activation of tumor necrosis factor-alpha (TNF-alpha)/interleukin-1 beta (IL-1 beta)/interleukin-6 (IL-6)/cyclooxygenase-2 (COX-2) inflammatory signaling was significantly abrogated in KO mice. Treatment with recombinant HDGF (rHDGF) dose-dependently stimulated the expression of TNF-alpha/IL-1 beta/IL-6/COX-2 in hepatocytes, further supporting the pro-inflammatory function of HDGF. Finally, application of HDGF antibody not only attenuated the ConA-mediated inflammatory cascade in hepatocytes, but also ameliorated the ConA-induced hepatic necrosis and AST elevation in mice. In summary, HDGF participates in ConA-induced hepatitis via neutrophils recruitment and may constitute a therapeutic target for acute hepatitis.

引用

页码：16163 / 16178

页数：16

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