Molecular Mechanisms in Chronic Pancreatitis

Zusammenfassung

Die Pathogenese der chronischen Pankreatitis wird gegenwärtig kontrovers diskutiert. Keines der vorgeschlagenen Modelle kann einen überzeugenden Zusammenhang zwischen den bekannten ätiologischen Faktoren (Alkohol-Abusus, metabolische Störungen, angeborene oder erworbene Pankreasgangobstruktionen) und den komplexen morphologischen und pathosphysiologischen Aspekten dieser Erkrankung herstellen. Jedoch hat die molekular- und zellbiologische Forschung in den letzten Jahren gezeigt, dass eine fehlgeleitete Immunantwort zusammen mit aktiv beteiligten Pankreas-Parenchymzellen zu Gewebezerstörung, Gewebeumbau und Fibrose führt. Die Infiltration des Pankreas durch bestimmte Subgruppen von Immunzellen, eine fehlgeleitete und verstärkte Exprimierung von MHC-Molekülen, sowie eine Überexprimierung von Wachstumsfaktoren und deren Rezeptoren spielen alle eine wichtige Rolle in der Pathogenese der chronischen Pankreatitis. Zusätzlich sind durch genetische Untersuchungen Gene identifiziert worden, welche Patienten zur Entwicklung einer chronischen Pankreatitis prädisponieren. Diese Forschungsergebnisse haben insbesondere neue Erkenntnisse hinsichtlich der Beziehung der chronischen Pankreatitis zum Pankreaskarzinom erbracht.

Summary

The pathogenesis of chronic pancreatitis (CP) is still controversial. None of the proposed models has been able to provide a convincing link between the known etiological factors - alcohol abuse, metabolic disturbances, congenital or acquired obstruction of the duct system - and the complex morphological and pathophysiological aspects of the disease. Molecular and cell biology research during the last years, however, has elucidated that a dysregulated immune response, together with an active involvement of pancreatic parenchymal cells, contributes to tissue destruction, fibrosis and remodeling in CP. Infiltration of the pancreas by particular subsets of immune effector cells, aberrant and enhanced expression of MHC molecules, and overexpression of growth factors and their receptors have all recently been found to play a role in CP. In addition, genetic analysis has led to the discovery of genes that predispose their carriers to the development of the disease, and has shed new light on the relation between CP and pancreatic cancer.

Schlüsselwörter

Chonische Pankreatitis - Wachstumsfaktoren - Wachstumsfaktorrezeptoren - Pathogenese

Key words

Chronic pancreatitis - Growth-factors - Growth-factor receptors - Pathogenesis

References

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