Abstract
Bone morphogenetic protein (BMP) signaling is active in many tissues including the central nervous system, in which it regulates cell proliferation, differentiation and maturation. The modulation of BMP pathway is crucial since abnormality of BMP signaling may cause cellular malfunction such as apoptosis. There are evidences indicating that miR-17 family is involved in the BMP signaling. In the present study, we demonstrated that BMP2 stimulation directly increased the transcription of miR-17-92 and miR-106b-25 cluster via Smad activation, which leads to the up-regulation of mature miR-17/20a/93. In addition, we provided evidence that BMP2 activation repressed BMPRII expression through modulating miR-17 family in primary neurons. Furthermore, we proved that such negative regulation protected neurons from apoptosis induced by abnormal BMP signaling. Taken together, these results suggest a regulatory pathway of BMP-miR-17 family-BMPRII, which consist a negative feedback loop that balances BMP signaling and maintains cell homeostasis in neurons.
Highlights
Bone morphogenetic protein (BMP) (Bone Morphogenetic Proteins) are a large subclass of the TGF-β (Transforming Growth Factor-β) super family, which have crucial roles in many tissues as well as neural system [1,2]
We examined the expression level of the miR-17/20a/93 in primary cortical neurons activated with BMP2 (10 ng/ml) and showed that all those miRNAs increased after the treatment (Figure 1B)
We demonstrated that pri-miR-17-92 and pri-miR-106b-25 were both up-regulated (~3 folds) upon BMP2 treatment, to mature miR-17/20a/93, suggesting that BMP2 stimulation increased the transcription of these two clusters (Figure 1B)
Summary
BMPs (Bone Morphogenetic Proteins) are a large subclass of the TGF-β (Transforming Growth Factor-β) super family, which have crucial roles in many tissues as well as neural system [1,2]. There are substantial evidences that BMP signaling plays a crucial role in the neural development including proliferation, differentiation and maturation [5,6,7]. Activation of Smad pathway through BMP2 or 4 facilitates the axonal growth in adult sensory neurons [10,11]. It is reported that aberrant activation of BMP signaling can cause neuronal dysfunction which may lead to further disorders [12,13]. It is of great significance to avoid the abnormality of BMP signaling in nervous system
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