Pepsin Secretion, Pepsinogen, and Gastrin in “Barrett's Esophagus”

Mangla, Jagdish C.; Schenk, Eric A.; Desbaillets, L.; Guarasci, Gilda; Kubasik, Norman P.; Turner, Michael D.

doi:10.1016/s0016-5085(76)80253-3

Cited by 48 publications

(8 citation statements)

References 16 publications

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“…Given that similar immunohistochemical markers, DNA content abnormalities, and rates of progression to dysplasia and malignancy have been observed in CLE, irrespective of goblet cell presence, considerable controversy exists regarding the use of goblet cells as diagnostic criteria for BE or inclusion criteria for EAC screening . Several CLE‐positive cases in this study expressed pepsinogen and gastric H+/K+‐ATPase proton pump mRNA, consistent with previous reports of pepsin and acid production in BE . Both heterotopic gastric mucosa in the esophagus and BE contain diverse cell types, including oxyntocardiac mucosa characterized by parietal (acid secreting) and chief (pepsin secreting) cells .…”

Section: Discussionsupporting

confidence: 90%

“…2 Several CLE-positive cases in this study expressed pepsinogen and gastric H+/K+-ATPase proton pump mRNA, consistent with previous reports of pepsin and acid production in BE. 31 Both heterotopic gastric mucosa in the esophagus and BE contain diverse cell types, including oxyntocardiac mucosa characterized by parietal (acid secreting) and chief (pepsin secreting) cells. 30,51 Evidence suggests that oxyntocardiac mucosa is a precursor of intestinal metaplasia and EAC, 52 and it is commonly found in the background of EAC as observed herein.…”

Section: Discussionmentioning

confidence: 99%

“…The gastric enzyme pepsin has previously been shown to promote chronic inflammation and carcinogenesis in the upper airways during extraesophageal reflux, which is typically weak or nonacidic and similar to that of patients taking PPIs . Furthermore, parietal and chief cells observed in BE, in the background of EAC and in heterotopic gastric mucosa patches in the esophagus, represent a potential source of locally synthesized pepsin and acid that may contribute to disease progression . We recently reported pepsinogen synthesis in BE mucosa in a small cohort of BE patients, and demonstrated pepsin‐induced inflammatory changes in esophageal cells in vitro .…”

Section: Introductionmentioning

confidence: 92%

“…[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Furthermore, parietal and chief cells observed in BE, in the background of EAC and in heterotopic gastric mucosa patches in the esophagus, represent a potential source of locally synthesized pepsin and acid that may contribute to disease progression. [30][31][32][33] We recently reported pepsinogen synthesis in BE mucosa in a small cohort of BE patients, and demonstrated pepsin-induced inflammatory changes in esophageal cells in vitro. 25 The purpose of this study was to continue investigation of the contribution of pepsin to molecular and morphological changes associated with BE and EAC in vitro, and to survey esophageal pepsinogen and gastric proton pump synthesis in clinical specimens from the normal-metaplasia-adenocarcinoma spectrum.…”

Section: Introductionmentioning

confidence: 99%

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Esophageal pepsin and proton pump synthesis in barrett's esophagus and esophageal adenocarcinoma

et al. 2019

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Objectives/Hypothesis Gastroesophageal reflux disease and associated metaplasia of the esophagus (Barrett's esophagus [BE]) are primary risk factors for esophageal adenocarcinoma (EAC). Widespread use of acid suppression medications has failed to stem the rise of EAC, suggesting that nonacid reflux may underlie its pathophysiology. Pepsin is a tumor promoter in the larynx and has been implicated in esophageal carcinogenesis. Herein, specimens from the esophageal cancer spectrum were tested for pepsin presence. Pepsin‐induced carcinogenic changes were assayed in an esophageal cell culture model. Study Design Laboratory analysis. Methods Pepsin was assayed in reflux and cancer free esophagi, BE, EAC, and esophageal cancer lacking association with reflux (squamous cell carcinoma [SCC]). Refluxed or locally synthesized pepsin was assayed by Western blot. Local synthesis of pepsin and proton pumps was assayed via reverse transcription–polymerase chain reaction. The effect of pepsin on BE and EAC markers was investigated via enzyme‐linked immunosorbent assay and quantitative polymerase chain reaction in human esophageal epithelial cells treated with pepsin or control diluent. Results Pepsinogen and proton pump mRNA were observed in BE (3/5) and EAC (4/4) samples, but not in normal adjacent specimens, SCC (0/2), or reflux and cancer‐free esophagi. Chronic pepsin treatment (0.1–1 mg/mL, 4 weeks) of human esophageal cells in vitro induced BE and EAC markers interleukin 8 and KRT8 and depleted normal esophageal marker KRT10 (P < .05) expression. Conclusions Local synthesis of pepsin and proton pumps in BE and EAC is not uncommon. Absence of these molecules in normal (noncancer) esophagi, SCC, and in vitro data support a role for pepsin in reflux‐attributed carcinogenic changes in the esophagus. Level of Evidence NA Laryngoscope, 129:2687–2695, 2019

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Esophageal pepsin and proton pump synthesis in barrett's esophagus and esophageal adenocarcinoma

et al. 2019

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“…The presence of gastric acid proteases in Barrett epithelium was demonstrated by Mangla et al (1973Mangla et al ( , 1976Mangla et al ( , 1980. Electrophoretically, eight fractions of acid proteases are identified in human gastric mucosal extracts, named pepsinogens (Pgl-Pg7) and slow moving protease (SMP) (Samloff 1969).…”

mentioning

confidence: 89%

Differential expression of pepsinogen isozymogens in a patient with Barrett esophagus

et al. 1988

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The pepsinogen A (PGA) isozymogens in the gastric mucosa and Barrett epithelium of a female patient with Barrett esophagus were studied on different occasions during a 3‐year period by electrophoretic analysis of in vivo steady‐state pepsinogen in biopsies by activity staining in combination with variant specific monoclonal antibodies and of de novo synthesized pepsinogen by autoradiography. In Barrett epithelium only one (Pg3) or two (Pg3 and Pg5) primary PGA gene products were detected, whereas in gastric mucosal biopsies three (Pg3, Pg4 and Pg5) primary gene products were demonstrated on all occasions. These differences strongly suggest differential expression/activation of individual gene numbers in the PGA gene cluster in Barrett esophagus and are in line with the preneoplastic nature of this condition. The mechanism behind this deregulation is currently under investigation by cell biology and molecular genetic techniques.

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Barrett's Ulcer and Treatment With Cimetidine

Kothari¹

1980

Arch Intern Med

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Pepsin Secretion, Pepsinogen, and Gastrin in “Barrett's Esophagus”

Cited by 48 publications

References 16 publications

Esophageal pepsin and proton pump synthesis in barrett's esophagus and esophageal adenocarcinoma

Esophageal pepsin and proton pump synthesis in barrett's esophagus and esophageal adenocarcinoma

Differential expression of pepsinogen isozymogens in a patient with Barrett esophagus

Barrett's Ulcer and Treatment With Cimetidine

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