Expression level of sonic hedgehog correlated with the speed of gastric mucosa regeneration in artificial gastric ulcers
Takeshi Tanaka
Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorCorresponding Author
Makoto Arai
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Correspondence
Dr Makoto Arai, Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chiba 260-8670, Japan. Email: [email protected]
Search for more papers by this authorShoko Minemura
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorArata Oyamada
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorKeiko Saito
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorXia Jiang
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorMasaru Tsuboi
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorSayuri Sazuka
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorDaisuke Maruoka
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorTomoaki Matsumura
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorTomoo Nakagawa
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorShigeru Sugaya
Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorTatsuo Kanda
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorTatsuro Katsuno
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorKazuko Kita
Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorTakashi Kishimoto
Department of Molecular Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorFumio Imazeki
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorAtsushi Kaneda
Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorOsamu Yokosuka
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorTakeshi Tanaka
Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorCorresponding Author
Makoto Arai
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Correspondence
Dr Makoto Arai, Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chiba 260-8670, Japan. Email: [email protected]
Search for more papers by this authorShoko Minemura
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorArata Oyamada
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorKeiko Saito
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorXia Jiang
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorMasaru Tsuboi
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorSayuri Sazuka
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorDaisuke Maruoka
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorTomoaki Matsumura
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorTomoo Nakagawa
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorShigeru Sugaya
Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorTatsuo Kanda
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorTatsuro Katsuno
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorKazuko Kita
Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorTakashi Kishimoto
Department of Molecular Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorFumio Imazeki
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorAtsushi Kaneda
Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorOsamu Yokosuka
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for more papers by this authorAbstract
Background and Aim
Gastric ulcer healing is a complex process involving cell proliferation and tissue remodeling. Sonic hedgehog (Shh) activates the Shh signaling pathway, which plays a key role in processes such as tissue repair. Shh and interleukin 1β (IL1β) have been reported to influence the proliferation of gastric mucosa. We evaluated the relationships between the speed of gastric ulcer healing and the levels of expression of Shh and IL1β.
Methods
The study included 45 patients (mean age 71.9 ± 9.0 years; M/F, 30/15) who underwent endoscopic submucosal dissection (ESD) for gastric cancer, followed by standard dose of oral proton-pump inhibitor for 4 weeks. Subsequently, the size of ESD-induced artificial ulcers were measured to determine the speed of gastric ulcer healing, and regenerating mucosa around the ulcers and appropriately matched controls were collected from patients by endoscopic biopsy. Polymerase chain reaction (PCR) array analysis of genes in the Shh signaling pathway was performed, and quantitative reverse transcription (RT)-PCR was used to measure IL1β mRNA.
Results
The levels of Shh and IL1β mRNA were 3.0 ± 2.7-fold and 2.5 ± 2.5-fold higher, respectively, in regenerating mucosa of artificial ulcers than in appropriately matched controls, with the two being positively correlated (r = 0.9, P < 0.001). Shh (r = 0.8, P < 0.001) and IL1β (r = 0.7, P < 0.005) expression was each positively correlated with the speed of gastric ulcer healing, but multivariate analysis showed that Shh expression was the only significant parameter (P = 0.045).
Conclusions
Expression of Shh was correlated with the speed of gastric ulcer healing, promoting the regeneration of gastric mucosa.
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