Acinar cell injury induced by inadequate unfolded protein response in acute pancreatitis
| Autor: | Kaylene Barrera, Devon John, Cathy M. Mueller, Chongmin Huan, Antonio E. Alfonso, Kei Okochi, Zuzanna Niewiadomska, Peiqi Ou, Albert Stanek, Scott Tenner |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
business.industry Endoplasmic reticulum Autophagy Review medicine.disease digestive system Acute pancreatitis Unfolded protein response Pathogenesis 03 medical and health sciences 030104 developmental biology Acinar cell injury Endoplasmic reticulum stress Cancer research medicine Acinar cell Signal transduction business Flux (metabolism) |
| Zdroj: | World Journal of Gastrointestinal Pathophysiology |
| ISSN: | 2150-5330 |
| DOI: | 10.4291/wjgp.v9.i2.37 |
| Popis: | Acute pancreatitis (AP) is an inflammatory disorder of pancreatic tissue initiated in injured acinar cells. Severe AP remains a significant challenge due to the lack of effective treatment. The widely-accepted autodigestion theory of AP is now facing challenges, since inhibiting protease activation has negligible effectiveness for AP treatment despite numerous efforts. Furthermore, accumulating evidence supports a new concept that malfunction of a self-protective mechanism, the unfolded protein response (UPR), is the driving force behind the pathogenesis of AP. The UPR is induced by endoplasmic reticulum (ER) stress, a disturbance frequently found in acinar cells, to prevent the aggravation of ER stress that can otherwise lead to cell injury. In addition, the UPR's signaling pathways control NFκB activation and autophagy flux, and these dysregulations cause acinar cell inflammatory injury in AP, but with poorly understood mechanisms. We therefore summarize the protective role of the UPR in AP, propose mechanistic models of how inadequate UPR could promote NFκB's pro-inflammatory activity and impair autophagy's protective function in acinar cells, and discuss its relevance to current AP treatment. We hope that insight provided in this review will help facilitate the research and management of AP. |
| Databáze: | OpenAIRE |
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