Pepsin in Gastric Fluid Promotes Epithelial Mesenchymal Transformation: Implications for Understanding the Role of Reflux in Pulmonary Fibrosis.

Ahmad, Fawzia; Ritzenthaler, Jeffrey D.; Roman, Jesse

doi:10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a5311

Cited by 7 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 72 Both acid and non-acid components of the reflux have been associated with worse pulmonary involvement. These clinical data are interestingly consistent with pre-clinical studies showing that EMT in lung tissue can be determined in animal models where pepsin, 73 biliary acid 74 or acid solution 75 are delivered to the lungs via aspiration.…”

Section: Alveolar Emt In Ssc-ild Patients and Preclinical Modelssupporting

confidence: 84%

Alveolar epithelial-to-mesenchymal transition in scleroderma interstitial lung disease: Technical challenges, available evidence and therapeutic perspectives

Lorenzis

Wasson

Galdo

2023

Journal of Scleroderma and Related Disorders

View full text Add to dashboard Cite

The alveolar epithelial-to-mesenchymal transition is the process of transformation of differentiated epithelial cells into mesenchymal-like cells through functional and morphological changes. A partial epithelial-to-mesenchymal transition process can indirectly contribute to lung fibrosis through a paracrine stimulation of the surrounding cells, while a finalized process could also directly enhance the pool of pulmonary fibroblasts and the extracellular matrix deposition. The direct demonstration of alveolar epithelial-to-mesenchymal transition in scleroderma-related interstitial lung disease is challenging due to technical pitfalls and the limited availability of lung tissue samples. Similarly, any inference on epithelial-to-mesenchymal transition occurrence driven from preclinical models should consider the limitations of cell cultures and animal models. Notwithstanding, while the occurrence or the relevance of this phenomenon in scleroderma-related interstitial lung disease have not been directly and conclusively demonstrated until now, pre-clinical and clinical evidence supports the potential role of epithelial-to-mesenchymal transition in the development and progression of lung fibrosis. Evidence consolidation on scleroderma-related interstitial lung disease epithelial-to-mesenchymal transition would pave the way for new therapeutic opportunities to prevent, slow or even reverse lung fibrosis, drawing lessons from current research lines in neoplastic epithelial-to-mesenchymal transition.

show abstract

Section: Alveolar Emt In Ssc-ild Patients and Preclinical Modelssupporting

confidence: 84%

Alveolar epithelial-to-mesenchymal transition in scleroderma interstitial lung disease: Technical challenges, available evidence and therapeutic perspectives

Lorenzis

Wasson

Galdo

2023

Journal of Scleroderma and Related Disorders

View full text Add to dashboard Cite

show abstract

“…In-vitro studies have shown that human airway epithelial cells exposed to unconjugated bile salts produce increased levels of the fibrogenic cytokine Transforming Growth Factor-β1 [ 30 ]. There is also preliminary data to suggest that airway epithelial cells exposed to pepsin can undergo epithelial-mesenchymal transformation, a process which is implicated in the pathogenesis of IPF [ 31 ]. In this context, our finding of frequent proximal reflux events in IPF subjects might be important because it demonstrates a potential mechanism by which alveolar epithelial cells could come into contact with the many components of gastric juice outlined above.…”

Section: Discussionmentioning

confidence: 99%

Effect of acid suppression therapy on gastroesophageal reflux and cough in idiopathic pulmonary fibrosis: an intervention study

Kilduff

Counter

Thomas

et al. 2014

Cough

View full text Add to dashboard Cite

BackgroundChronic cough affects more than 70 percent of patients with Idiopathic Pulmonary Fibrosis and causes significant morbidity. Gastroesophageal reflux is the cause of some cases of chronic cough; and also has a postulated role in the aetiology of Idiopathic Pulmonary Fibrosis. A high prevalence of acid; and more recently non-acid, reflux has been observed in Idiopathic Pulmonary Fibrosis cohorts. Therefore, gastroesophageal reflux may be implicated in the pathogenesis of cough in Idiopathic Pulmonary Fibrosis.MethodsEighteen subjects with Idiopathic Pulmonary Fibrosis underwent 24-hour oesophageal impedance and cough count monitoring after the careful exclusion of causes of chronic cough other than gastroesophageal reflux. All 18 were then treated with high dose acid suppression therapies. Fourteen subjects underwent repeat 24-hour oesophageal impedance and cough count monitoring after eight weeks.ResultsTotal reflux and acid reflux frequencies were within the normal range in the majority of this cohort. The frequencies of non-acid and proximal reflux events were above the normal range. Following high dose acid suppression therapy there was a significant decrease in the number of acid reflux events (p = 0.02), but an increase in the number of non-acid reflux events (p = 0.01). There was no change in cough frequency (p = 0.70).ConclusionsThis study confirms that non-acid reflux is prevalent; and that proximal oesophageal reflux occurs in the majority, of subjects with Idiopathic Pulmonary Fibrosis. It is the first study to investigate the effect of acid suppression therapy on gastroesophageal reflux and cough in patients with Idiopathic Pulmonary Fibrosis. The observation that cough frequency does not improve despite verifiable reductions in oesophageal acid exposure challenges the role of acid reflux in Idiopathic Pulmonary Fibrosis associated cough. The finding that non-acid reflux is increased following the use of acid suppression therapies cautions against the widespread use of acid suppression in patients with Idiopathic Pulmonary Fibrosis given the potential role for non-acid reflux in the pathogenesis of cough and Idiopathic Pulmonary Fibrosis itself.Study registrationThe study was registered with the Cardiff and Vale University Local Health Board Research and Development Committee (09/CMC/4619) and the South East Wales Ethics Committee (09/WSE04/57).

show abstract

“…In-vitro studies have shown that airway epithelial cells exposed to unconjugated bile salts produce increased levels of the fibrogenic cytokine Transforming Growth Factor-β1 [30]. There is also preliminary data to suggest that airway epithelial cells exposed to pepsin can undergo epithelial-mesenchymal transformation, a process which may be associated with the pathogenesis of IPF [31]. …”

Section: Sarcoidosismentioning

confidence: 99%

Cough, sarcoidosis and idiopathic pulmonary fibrosis: raw nerves and bad vibrations

Harrison

2013

Cough

View full text Add to dashboard Cite

Cough is a common symptom in people who develop interstitial lung diseases (ILD). The pathological features of the ILDs are many and varied suggesting that the cause of cough may also vary with each disease. This article reviews what is currently known about cough in sarcoidosis and idiopathic pulmonary fibrosis; two of the commonest ILDs. It also outlines some of the theories which have been proposed to explain why cough develops in these conditions and describes what little is known about how to treat it.

show abstract

Pepsin in Gastric Fluid Promotes Epithelial Mesenchymal Transformation: Implications for Understanding the Role of Reflux in Pulmonary Fibrosis.

Cited by 7 publications

References 0 publications

Alveolar epithelial-to-mesenchymal transition in scleroderma interstitial lung disease: Technical challenges, available evidence and therapeutic perspectives

Alveolar epithelial-to-mesenchymal transition in scleroderma interstitial lung disease: Technical challenges, available evidence and therapeutic perspectives

Effect of acid suppression therapy on gastroesophageal reflux and cough in idiopathic pulmonary fibrosis: an intervention study

Cough, sarcoidosis and idiopathic pulmonary fibrosis: raw nerves and bad vibrations

Contact Info

Product

Resources

About