In a study of a fragment of a synthetic of rat PGC, Kishi et al. This suggested that PGC played a role in healing of the gastric mucosa [ 15 ]. Minn et al. Synthetic human or monkey PGC had similar activity, which indicated that these polypeptides might have an antimicrobial effect on the gastrointestinal mucosa [ 16 ]. Gerson et al. PGC is also a valuable marker for distinguishing transdifferentiated type 1 epithelial cells [ 3 ].
These evidence indicate that PGC also plays a major role in lung maturation. Sorensen et al. The enzyme activation following exposure of the antimicrobial peptides in seminal fluid to the vaginal fluids indicated that PGC was involved in the mechanism of infection prevention after sexual intercourse [ 18 ]. In addition, PGC might also function in reproduction. Szecsi et al. These processes contribute to the prevention of immune infertility [ 19 ].
Dos Reis et al. Proteolytic enzymes are associated with tumour invasion and metastasis. Similar to other proteases such as matrix metalloproteinase and plasminogen activator, PGC might exert its dissolving function in tumour cells [ 20 ].
The schema chart of potential physiological functions of PGC was drawn in Fig. Potential physiological functions of PGC. The functions of PGC includes digesting proteins, promoting the healing of gastric mucosa, maturing of organs, antimicrobial effect of gastric mucosa, preventing immune infertility and infection after intercourse, and degrading extracellular matrix.
Many other functions of PGC are still unknown. Human PGC is expressed in at least three forms, including gastric mucosal in situ, serum and ectopic expression.
Under pathological conditions, PGC expression levels change significantly and correlate closely with cancer development and progression. PGC in situ expression occurs mainly in the normal gastric mucosa and the expression is decreased or absent during GC development. Ning et al. These findings suggested that PGC in situ expression levels correlated negatively with GC occurrence.
Melle et al. Xu et al. Tatematsu et al. Steele et al. Thus, PGC could serve as a symbol of primary gastric epithelial cells. In addition, Stemmermann et al. A possible reason for PGC positive expression in intestinal metaplasia—related tumours may be that the residual normal stomach glandular bodies or intestinal metaplasia cells induced a gastric phenotype mutation [ 27 ].
Fernadez et al. They found Thus, they concluded that PGC expression is an independent prognostic factor [ 28 ]. Once H. He et al. The cut-off values of serum PGC varied by geographic region and ethnicity [ 30 ]. Serum PGC could serve as an effective biomarker for monitoring changes in gastric morphology before and after the eradication of H. Massarrat et al. Using enzyme-linked immunosorbent assay, Sun et al. Therefore, serum PGC detection is suitable for determining the eradication efficacy of H.
Kiyohira et al. Serum PGC serves as a biomarker of gastric mucosa morphology and precancerous lesions. Samloff et al.
Miki et al. Sun et al. Tu et al. Xie et al. This method for PGC detection has great application value for early screening of GC patients, therapeutic evaluation, and real-time dynamic monitoring of GC progression.
The multi-index prediction model can be used to predict risk of GC more accurately and effectively. Cao et al. Huang et al. The sensitivity and specificity for screening AG was 0.
More recently, Yeh et al. The results indicated that the risk of intestinal-type NCGA could be reduced by screening the general population at 50 years of age as follows: serum PG screening, Consequently, serum PG screening was more effective than the other methods. It was an efficient measure for decreasing the mortality rate of smokers with intestinal metaplasia—type NCGA in the high-risk GC group.
Accordingly, a more ideal sequential screening strategy should start with serum PG detection, followed by endoscopic biopsy to screen the positive results. This could contribute to distinguish high-risk individuals from low-risk individuals to ensure that they will benefit from subsequent therapy [ 42 ].
Serum PGC is related with cancers of other organs beyond initial gastric diseases. Ito et al. Yada et al. As the patients did not have any obvious gastric inflammation, atrophic changes or H. The preoperative aberrant elevated serum PGC may be due to obstruction of the duodenal Brunner glands by the large duodenal tumour, and PGC was more likely to be secreted to the circulation [ 44 ].
Although PGC expression in vivo is mainly in the stomach, there are several reports on ectopic PGC expression in extragastric organs such as the prostate, lungs and seminal vesicles [ 2 , 3 , 4 ]. PGC expression levels were apparently promoted, especially in the tumour, for example, in prostate cancer, breast cancer, ovary cancer, endometrial cancer, pancreatic cancer, kidney cancer, bladder cancer, eyelid basal cell carcinoma, squamous cell carcinoma and melanoma, etc.
It is worth noting that in sex-related tumours such as prostate cancer, breast cancer and ovary cancer, PGC expression is increased in cancer tissues as compared to normal tissues. Using immunohistochemistry, Diaz et al. Antunes et al.
Serra et al. As an aspartic protease, PGC might contribute to the decomposition of invasive breast cancer lesions [ 6 , 7 ]. The consensus is that PGC expression in breast cancer cells might represent good prognosis. A possible explanation for this is that the presence of PGC may affect hormone receptor pathways.
Balbin et al. The observed extragastric expression of PGC may be a consequence of the ability of this gene to respond to the hormonal stimuli, including androgens, glucocorticoids, and progesterone [ 51 ]. Rojo et al. Tenti et al. Rothacker et al. Fukushima et al. Miyasaka et al. Nakamura et al. And downregulating PGC caused tumour cell dedifferentiation or deterioration, which is closely related with cancer prognosis and metastasis [ 56 ].
The regulation of gene expression refers to a regulative progress of a gene expressed from DNA to protein. And the regulation of PGC expression involves genetic and epigenetic alteration of the encoding gene, hormones control and interactions between PGC with other transcription factors and protein kinases Fig.
The regulation of PGC expression. The regulation of PGC expression involves genetic and epigenetic alteration of the encoding gene, hormones modulation and interactions between PGC with other transcription factors and protein kinases.
Human PGC is a In , Azuma et al. Based on the fragment lengths, four alleles with different molecular weights were obtained following agarose gel electrophoresis of PCR products: allele 1 bps allele 2 bps , allele 3 bps and allele 4 bps [ 57 ].
Liu et al. In recent years, Kumarh as used similar methods and reached further conclusions that PGC homozygous allele 1 may elevate serum PGC levels in patients with GC, especially in patients with H.
However, Pinto-Correia reported that PGC homozygous allele 1 was related to the up-regulation of PGC expression to serve as a protective factor in the development of gastric disease [ 61 ].
Besides, two other SNPs, rs and rs were reported to play a part in upregulating PGC expression [ 62 , 63 , 64 ]. Altered PGC expression could at least in part reveal the correlation between individuals with specific genetic variants and GC risk. Epigenetic factors, including methylation, acetylation and non-coding RNA, play a crucial role in regulating gene expression. Numerous studies have confirmed that the hypermethylation of a tumour suppressor gene decreases its coding protein expression and subsequent tumorigenesis.
The gastric mucosa of non-cancerous rats and untreated rats were not methylated [ 65 ]. Acetylation also affects the expression of PGC. Perlmann et al. Acetylation of pepsinogen led to a reduced susceptibility of activation, which was reflected through a decreased hydrolysis of the synthetic substrate.
Compared to pepsin, the lysine and tyrosine residues of acetylated pepsinogen were acetylated. Therefore, pepsin acetylation was involved in the essential functional groups of enzyme activity, while pepsinogen acetylation mainly affects the conformational characteristics of the molecule [ 66 ].
Serum let-7c is negatively related to PGC gene expression [ 67 ]. The serum let-7c of individuals with H. In sex-related tumours such as prostate cancer, breast cancer and ovary cancer, PGC upregulation is an indicator that hormones might play a vital role in regulating PGC expression.
Androgen, glucocorticoids and progesterone induced PGC upregulation in breast cancer cells. Incubating breast cancer cells with dihydrotestosterone, progesterone or the synthetic glucocorticoid dexamethasone for 48 h could induce 1. Such a hypothesis may be deduced from PGC expression in breast cancer and cysts but not in normal glands. PGC may serve as a biomarker of hormone imbalance under these pathological conditions, reflecting the presence of tumour-associated hormone receptor pathways.
Noburo et al. Similarly, in vitro experiments have verified the changes in PGC expression under hormone alteration. Wells et al. The findings demonstrated the role of IEC-6 cells as a model of PGC expression in vitro and in the small intestine [ 72 ]. Ishihara screened the rat PGC gene using a probe, and found that PGC expression was increased after hydrocortisone injection [ 73 ]. Furthermore, adding caffeine for a further 24 h induction resulted in a more notable increase in PGC mRNA levels [ 74 ].
It could speculate that glucocorticoids influence human cell maturation and differentiation and increase PGC expression.
The role of hormones such as glucocorticoids, growth factor and hepatocyte growth factor, and mesenchymal interactions are of vital importance for chief cell differentiation. Glucocorticoids influence the gastric epithelial cell proliferation and differentiation in vivo, and might inhibit morphological changes to promote PG gene expression. Hydrocortisone treatment of rat gastric explant cells stimulated differentiation, and PG was synthesised.
Therefore, glucocorticoid is an important regulatory factor of PGC and of chief cell function and differentiation [ 75 ]. Interactions between PGC with other transcription factors or protein kinases are also involved in the regulation of PGC expression. Sakamoto et al. GATA-5 was highly expressed in chicken gastric mucosa, and efficiently upregulates luciferase gene expression through cis-acting elements. In addition, chicken PGC expression was associated with epithelial—mesenchymal transition [ 76 , 77 ].
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This article is also available for rental through DeepDyve. View Metrics. Email alerts Article activity alert. Advance article alerts. New issue alert. Digestion starts with the sight, thought, or smell of food. When the brain anticipates an incoming meal, the vagus nerve sends a message to the stomach causing the release of acetylcholine.
The binding of acetylcholine to G cells in the stomach starts the secretion of gastrin and, in combination with acetylcholine and histamine, stimulates parietal cells in the gastric glands of the stomach body to start secreting hydrochloric acid HCl.
Acid in the stomach serves several purposes but is mostly associated with degrading proteins and polysaccharides so they can cross the intestinal epithelium.
Approximately 2 L of HCl is produced daily. The pH level in the stomach ranges from 1. The pH of the stomach is regulated by a negative feedback loop by antral D cells that release somatostatin which inhibits the release of gastrin. Pepsinogen is secreted by chief cells in the gastric glands of the body and antrum of the stomach. Proteins are reduced to fragments of various sizes, called peptides, or amino acids, by pepsin so they can eventually be absorbed in the small intestine.
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