R-SMAD-dependent TGFandbeta; signalling mediates TGFandbeta; -in | 50177

Journal of Neurology & Neurophysiology

ISSN - 2155-9562

R-SMAD-dependent TGFβ signalling mediates TGFβ -induced effects on microglia

Joint Event on International Conference on Neuroimmunology, Neurological disorders and Neurogenetics & 28th World Summit on Neurology, Neuroscience and Neuropharmacology

September 26-27, 2018 | Montreal, Canada

Phani Sankar Potru, Tanza Zoller, Kerstin Krieglstein and Bjorn Spittau

University of Freiburg, Germany
University of Rostock, Germany

Posters & Accepted Abstracts: J Neurol Neurophysiol

Abstract :

Microglia are the resident immune cells of the central nervous system (CNS) which are exclusive conciliators of immune responses in CNS. Previously, it has been shown that TGFβ1 signaling is crucial in maintaining the resting state of microglia (Spittau et al., 2013) and that it also blocks LPS induced microglia activation. It is well established that TGFβ1 signaling requires formation of a complex between R-SMADs 2 and 3 and Co-SMAD4. However, our previous results suggested that microglia specific TGFβR2-/- results in impaired pSMAD2 mediated transcription but not in SMAD4-/- mouse model. To address this discrepancy, we performed subcellular fractionation and Co-immunoprecipitation analysis of BV-2 immortalized murine microglial cell line. Western blot analysis of protein fractions demonstrated the presence of pSMAD2 and SMAD2/3 in all the fractions. However, SMAD4 was undetectable in chromatin fraction despite the presence of SMAD2/3. The Co-IP results suggested a weak Smad 2/3 and Smad4 interaction irrespective of treatment. Non-canonical pathway analysis was performed using the PathScan Intracellular Signaling Array Kit. Surprisingly, no non-canonical pathway activation was detected in BV2 cells upon stimulation with TGFβ1. These results are going to further quantified by western blotting. Taken together, our data suggest that SMAD2/3 and SMAD4 are not necessarily interacting with each other upon stimulation with TGFβ1 in microglia. Our initial results also suggested a lack of non-canonical pathway activation in BV2 cells.

Biography :