Hepatoma-derived growth factor participates in Helicobacter Pylori-induced neutrophils recruitment, gastritis and gastric carcinogenesis

Tian Huei Chu; Shih Tsung Huang; Sheau Fang Yang; Chia Jung Li; Hung Wei Lin; Bi Chuang Weng; Shih Ming Yang; Shih Chung Huang; Jian Ching Wu; Yi Chen Chang; Zhi Hong Wen; Yi Ming Arthur Chen; Wen Jeng Wu; Mei Lang Kung; Po Han Tai; Deng Chyang Wu; Ming Hong Tai

doi:10.1038/s41388-019-0886-3

Hepatoma-derived growth factor participates in Helicobacter Pylori-induced neutrophils recruitment, gastritis and gastric carcinogenesis

Tian Huei Chu, Shih Tsung Huang, Sheau Fang Yang, Chia Jung Li, Hung Wei Lin, Bi Chuang Weng, Shih Ming Yang, Shih Chung Huang, Jian Ching Wu, Yi Chen Chang, Zhi Hong Wen, Yi Ming Arthur Chen, Wen Jeng Wu, Mei Lang Kung, Po Han Tai, Deng Chyang Wu, Ming Hong Tai

Research output: Contribution to journal › Article › peer-review

34 Citations (Scopus)

Abstract

Helicobacter pylori (Hp) infection and overexpression of hepatoma-derived growth factor (HDGF) are involved in gastric carcinogenesis. However, the relationship between Hp-induced gastric diseases and HDGF upregulation is not yet completely clear. This study aimed to elucidate the role of HDGF in Hp-induced gastric inflammation and carcinogenesis. HDGF expression in gastric biopsy and serum from patients was analyzed by immunohistochemical and ELISA analysis, respectively. Hp and gastric cells coculture system was employed to delineate the mechanism underlying HDGF overexpression during Hp infection. The gastric pathologies of wild type and HDGF knockout mice after Hp infection were investigated by immunohistochemical, immunoblot, and immunofluorescence analyses. HDGF level was significantly elevated in patients with Hp infection or intestinal metaplasia (IM, a precancerous lesion), and HDGF overexpression was positively correlated with Hp load, IM, and neutrophil infiltration in gastric biopsy. Consistently, patients with Hp infection or IM had significantly higher serum HDGF level. By using coculture assay, Hp infection led to HDGF upregulation and secretion in gastric cells. In mice model, HDGF ablation significantly suppressed the Hp-induced neutrophil infiltration and inflammatory TNF-α/COX-2 signaling, thereby relieving the tissue damage in stomach. This was further supported by that recombinant HDGF (rHDGF) stimulated the differentiation/chemotaxis of cultured neutrophils and oncogenic behaviors of gastric cells. Time series studies showed that Hp infection elicited an inflammatory TNF-α/HDGF/COX-2 cascade in stomach. HDGF secretion by Hp infection promotes the neutrophils infiltration and relays Hp-induced inflammatory signaling. Thus, HDGF may constitute a novel diagnostic marker and therapeutic target for Hp-induced gastritis and carcinogenesis.

Original language	English
Pages (from-to)	6461-6477
Number of pages	17
Journal	Oncogene
Volume	38
Issue number	37
DOIs	https://doi.org/10.1038/s41388-019-0886-3
Publication status	Published - Sept 12 2019
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41388-019-0886-3

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Chu, T. H., Huang, S. T., Yang, S. F., Li, C. J., Lin, H. W., Weng, B. C., Yang, S. M., Huang, S. C., Wu, J. C., Chang, Y. C., Wen, Z. H., Chen, Y. M. A., Wu, W. J., Kung, M. L., Tai, P. H., Wu, D. C., & Tai, M. H. (2019). Hepatoma-derived growth factor participates in Helicobacter Pylori-induced neutrophils recruitment, gastritis and gastric carcinogenesis. Oncogene, 38(37), 6461-6477. https://doi.org/10.1038/s41388-019-0886-3

Chu, TH, Huang, ST, Yang, SF, Li, CJ, Lin, HW, Weng, BC, Yang, SM, Huang, SC, Wu, JC, Chang, YC, Wen, ZH, Chen, YMA, Wu, WJ, Kung, ML, Tai, PH, Wu, DC & Tai, MH 2019, 'Hepatoma-derived growth factor participates in Helicobacter Pylori-induced neutrophils recruitment, gastritis and gastric carcinogenesis', Oncogene, vol. 38, no. 37, pp. 6461-6477. https://doi.org/10.1038/s41388-019-0886-3

@article{c775408c2362438fa776dc6745b42e8f,

title = "Hepatoma-derived growth factor participates in Helicobacter Pylori-induced neutrophils recruitment, gastritis and gastric carcinogenesis",

abstract = "Helicobacter pylori (Hp) infection and overexpression of hepatoma-derived growth factor (HDGF) are involved in gastric carcinogenesis. However, the relationship between Hp-induced gastric diseases and HDGF upregulation is not yet completely clear. This study aimed to elucidate the role of HDGF in Hp-induced gastric inflammation and carcinogenesis. HDGF expression in gastric biopsy and serum from patients was analyzed by immunohistochemical and ELISA analysis, respectively. Hp and gastric cells coculture system was employed to delineate the mechanism underlying HDGF overexpression during Hp infection. The gastric pathologies of wild type and HDGF knockout mice after Hp infection were investigated by immunohistochemical, immunoblot, and immunofluorescence analyses. HDGF level was significantly elevated in patients with Hp infection or intestinal metaplasia (IM, a precancerous lesion), and HDGF overexpression was positively correlated with Hp load, IM, and neutrophil infiltration in gastric biopsy. Consistently, patients with Hp infection or IM had significantly higher serum HDGF level. By using coculture assay, Hp infection led to HDGF upregulation and secretion in gastric cells. In mice model, HDGF ablation significantly suppressed the Hp-induced neutrophil infiltration and inflammatory TNF-α/COX-2 signaling, thereby relieving the tissue damage in stomach. This was further supported by that recombinant HDGF (rHDGF) stimulated the differentiation/chemotaxis of cultured neutrophils and oncogenic behaviors of gastric cells. Time series studies showed that Hp infection elicited an inflammatory TNF-α/HDGF/COX-2 cascade in stomach. HDGF secretion by Hp infection promotes the neutrophils infiltration and relays Hp-induced inflammatory signaling. Thus, HDGF may constitute a novel diagnostic marker and therapeutic target for Hp-induced gastritis and carcinogenesis.",

author = "Chu, {Tian Huei} and Huang, {Shih Tsung} and Yang, {Sheau Fang} and Li, {Chia Jung} and Lin, {Hung Wei} and Weng, {Bi Chuang} and Yang, {Shih Ming} and Huang, {Shih Chung} and Wu, {Jian Ching} and Chang, {Yi Chen} and Wen, {Zhi Hong} and Chen, {Yi Ming Arthur} and Wu, {Wen Jeng} and Kung, {Mei Lang} and Tai, {Po Han} and Wu, {Deng Chyang} and Tai, {Ming Hong}",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2019",

month = sep,

day = "12",

doi = "10.1038/s41388-019-0886-3",

language = "English",

volume = "38",

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T1 - Hepatoma-derived growth factor participates in Helicobacter Pylori-induced neutrophils recruitment, gastritis and gastric carcinogenesis

AU - Chu, Tian Huei

AU - Huang, Shih Tsung

AU - Yang, Sheau Fang

AU - Li, Chia Jung

AU - Lin, Hung Wei

AU - Weng, Bi Chuang

AU - Yang, Shih Ming

AU - Huang, Shih Chung

AU - Wu, Jian Ching

AU - Chang, Yi Chen

AU - Wen, Zhi Hong

AU - Chen, Yi Ming Arthur

AU - Wu, Wen Jeng

AU - Kung, Mei Lang

AU - Tai, Po Han

AU - Wu, Deng Chyang

AU - Tai, Ming Hong

PY - 2019/9/12

Y1 - 2019/9/12

N2 - Helicobacter pylori (Hp) infection and overexpression of hepatoma-derived growth factor (HDGF) are involved in gastric carcinogenesis. However, the relationship between Hp-induced gastric diseases and HDGF upregulation is not yet completely clear. This study aimed to elucidate the role of HDGF in Hp-induced gastric inflammation and carcinogenesis. HDGF expression in gastric biopsy and serum from patients was analyzed by immunohistochemical and ELISA analysis, respectively. Hp and gastric cells coculture system was employed to delineate the mechanism underlying HDGF overexpression during Hp infection. The gastric pathologies of wild type and HDGF knockout mice after Hp infection were investigated by immunohistochemical, immunoblot, and immunofluorescence analyses. HDGF level was significantly elevated in patients with Hp infection or intestinal metaplasia (IM, a precancerous lesion), and HDGF overexpression was positively correlated with Hp load, IM, and neutrophil infiltration in gastric biopsy. Consistently, patients with Hp infection or IM had significantly higher serum HDGF level. By using coculture assay, Hp infection led to HDGF upregulation and secretion in gastric cells. In mice model, HDGF ablation significantly suppressed the Hp-induced neutrophil infiltration and inflammatory TNF-α/COX-2 signaling, thereby relieving the tissue damage in stomach. This was further supported by that recombinant HDGF (rHDGF) stimulated the differentiation/chemotaxis of cultured neutrophils and oncogenic behaviors of gastric cells. Time series studies showed that Hp infection elicited an inflammatory TNF-α/HDGF/COX-2 cascade in stomach. HDGF secretion by Hp infection promotes the neutrophils infiltration and relays Hp-induced inflammatory signaling. Thus, HDGF may constitute a novel diagnostic marker and therapeutic target for Hp-induced gastritis and carcinogenesis.

AB - Helicobacter pylori (Hp) infection and overexpression of hepatoma-derived growth factor (HDGF) are involved in gastric carcinogenesis. However, the relationship between Hp-induced gastric diseases and HDGF upregulation is not yet completely clear. This study aimed to elucidate the role of HDGF in Hp-induced gastric inflammation and carcinogenesis. HDGF expression in gastric biopsy and serum from patients was analyzed by immunohistochemical and ELISA analysis, respectively. Hp and gastric cells coculture system was employed to delineate the mechanism underlying HDGF overexpression during Hp infection. The gastric pathologies of wild type and HDGF knockout mice after Hp infection were investigated by immunohistochemical, immunoblot, and immunofluorescence analyses. HDGF level was significantly elevated in patients with Hp infection or intestinal metaplasia (IM, a precancerous lesion), and HDGF overexpression was positively correlated with Hp load, IM, and neutrophil infiltration in gastric biopsy. Consistently, patients with Hp infection or IM had significantly higher serum HDGF level. By using coculture assay, Hp infection led to HDGF upregulation and secretion in gastric cells. In mice model, HDGF ablation significantly suppressed the Hp-induced neutrophil infiltration and inflammatory TNF-α/COX-2 signaling, thereby relieving the tissue damage in stomach. This was further supported by that recombinant HDGF (rHDGF) stimulated the differentiation/chemotaxis of cultured neutrophils and oncogenic behaviors of gastric cells. Time series studies showed that Hp infection elicited an inflammatory TNF-α/HDGF/COX-2 cascade in stomach. HDGF secretion by Hp infection promotes the neutrophils infiltration and relays Hp-induced inflammatory signaling. Thus, HDGF may constitute a novel diagnostic marker and therapeutic target for Hp-induced gastritis and carcinogenesis.

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JF - Oncogene

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ER -

Hepatoma-derived growth factor participates in Helicobacter Pylori-induced neutrophils recruitment, gastritis and gastric carcinogenesis

Abstract

ASJC Scopus subject areas

UN SDGs

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