Characterization of the Rat Oncostatin M Receptor Complex Which Resembles the Human, but Differs from the Murine Cytokine ReceptorReport as inadecuate




Characterization of the Rat Oncostatin M Receptor Complex Which Resembles the Human, but Differs from the Murine Cytokine Receptor - Download this document for free, or read online. Document in PDF available to download.

Evaluation of a pathophysiological role of the interleukin-6-type cytokine oncostatin M OSM for human diseases has been complicated by the fact that mouse models of diseases targeting either OSM or the OSM receptor OSMR complex cannot fully reflect the human situation. This is due to earlier findings that human OSM utilizes two receptor complexes, glycoprotein 130 gp130-leukemia inhibitory factor receptor LIFR type I and gp130-OSMR type II, both with wide expression profiles. Murine OSM on the other hand only binds to the gp130-OSMR type II receptor complex with high affinity. Here, we characterize the receptor usage for rat OSM. Using different experimental approaches knock-down of the OSMR expression by RNA interference, blocking of the LIFR by LIF-05, an antagonistic LIF variant and stably transfected Ba-F3 cells we can clearly show that rat OSM surprisingly utilizes both, the type I and type II receptor complex, therefore mimicking the human situation. Furthermore, it displays cross-species activities and stimulates cells of human as well as murine origin. Its signaling capacities closely mimic those of human OSM in cell types of different origin in the way that strong activation of the Jak-STAT, the MAP kinase as well as the PI3K-Akt pathways can be observed. Therefore, rat disease models would allow evaluation of the relevance of OSM for human biology.



Author: Johannes Drechsler, Joachim Grötzinger, Heike M. Hermanns

Source: http://plos.srce.hr/



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