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 | |
| Publication status | Published - Sep 12 2019 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research
Cite this
Hepatoma-derived growth factor participates in Helicobacter Pylori-induced neutrophils recruitment, gastritis and gastric carcinogenesis. / Chu, Tian Huei; Huang, Shih Tsung; Yang, Sheau Fang; Li, Chia Jung; Lin, Hung Wei; Weng, Bi Chuang; Yang, Shih Ming; Huang, Shih Chung; Wu, Jian Ching; Chang, Yi Chen; Wen, Zhi Hong; Chen, Yi Ming Arthur; Wu, Wen Jeng; Kung, Mei Lang; Tai, Po Han; Wu, Deng Chyang; Tai, Ming Hong.
In: Oncogene, Vol. 38, No. 37, 12.09.2019, p. 6461-6477.Research output: Contribution to journal › Article
}
TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=85070201948&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85070201948&partnerID=8YFLogxK
U2 - 10.1038/s41388-019-0886-3
DO - 10.1038/s41388-019-0886-3
M3 - Article
C2 - 31332288
AN - SCOPUS:85070201948
VL - 38
SP - 6461
EP - 6477
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 37
ER -