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Harumasa Yokota, Chiemi Matsumoto, Akito Shimouchi, Shoji Kimura, Hiroya Kobayashi, Akitoshi Yoshida; The role of the receptor-associated prorenin system in microglial activation. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):426.
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© ARVO (1962-2015); The Authors (2016-present)
Microglial activation is an early event that leads to neuronal degeneration in diabetic retinopathy (DR) even without overt vascular signs of retinopathy. The receptor associated prorenin system (RAPS) has been found to increase inflammation and oxidative stress in DR. However, the role of the RAPS in microglial activation is not determined yet. The aim of this study was to determine whether the RAPS was crucial for microglial activation or not.
Immunohistochemistry and quantitative RT-PCR were performed to confirm the presence of angiotensin II type 1 receptor (AT1R), type 2 receptor (AT2R) and (pro)renin receptor ((P)RR) in immortalized murine microglial cells (BV2 cells). BV2 cells were incubated with recombinant murine prorenin (10nM, 100nM) or angiotensin II (10nM, 100nM) in the presence or absence of siRNA-(P)RR. Pro-inflammatory cytokines TNF-α and IL-1β were analyzed with real time RT-PCR.
Both immunohistochemistry and quantitative RT-PCR clearly showed that AT1R, AT2R and (P)RR were expressed in BV2 cells. Prorenin stimulated cytokine expression in BV2 cells (2.5 fold for TNF-α; 6.5 fold for IL-1β in 100nM of prorenin concentration). Prorenin-stimulated increase of cytokine expression was attenuated by siRNA-(P)RR . In contrast, angiotensin II didn’t cause any alteration in the expression of pro-inflammatory cytokines.
Our data clearly demonstrated that prorenin, but not angiotensin II, stimulated microglia, which consequently produced pro-inflammatory cytokines. The mechanism underlying involvement of the RAPS in microglial activation is suggested to depend exclusively on angiotensin II-independent pathway.
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