Periostin Responds to Mechanical Stress and Tension by Activating the MTOR Signaling Pathway Rosselli-Murai, Luciana K. Almeida, Luciana O. Zagni, Chiara Galindo Moreno, Pablo Antonio Padial Molina, Miguel Volk, Sarah L. Murai, Marcelo J. Ríos, Héctor F. Squarize, Cristiane H. Castilho, Rogerio M. Cell migration Epithelial cells Fibroblasts Mechanical stress Raptors Small interfering RNA Tissue repair Wound heading Current knowledge about Periostin biology has expanded from its recognized functions in embryogenesis and bone metabolism to its roles in tissue repair and remodeling and its clinical implications in cancer. Emerging evidence suggests that Periostin plays a critical role in the mechanism of wound healing; however, the paracrine effect of Periostin in epithelial cell biology is still poorly understood. We found that epithelial cells are capable of producing endogenous Periostin that, unlike mesenchymal cell, cannot be secreted. Epithelial cells responded to Periostin paracrine stimuli by enhancing cellular migration and proliferation and by activating the mTOR signaling pathway. Interestingly, biomechanical stimulation of epithelial cells, which simulates tension forces that occur during initial steps of tissue healing, induced Periostin production and mTOR activation. The molecular association of Periostin and mTOR signaling was further dissected by administering rapamycin, a selective pharmacological inhibitor of mTOR, and by disruption of Raptor and Rictor scaffold proteins implicated in the regulation of mTORC1 and mTORC2 complex assembly. Both strategies resulted in ablation of Periostin-induced mitogenic and migratory activity. These results indicate that Periostin-induced epithelial migration and proliferation requires mTOR signaling. Collectively, our findings identify Periostin as a mechanical stress responsive molecule that is primarily secreted by fibroblasts during wound healing and expressed endogenously in epithelial cells resulting in the control of cellular physiology through a mechanism mediated by the mTOR signaling cascade. 2014-02-07T10:52:09Z 2014-02-07T10:52:09Z 2013 info:eu-repo/semantics/article Rosselli-Murai, L.K.; et al. Periostin Responds to Mechanical Stress and Tension by Activating the MTOR Signaling Pathway . Plos One, 8(12): e83580 (2013). [http://hdl.handle.net/10481/30300] 1932-6203 doi: 10.1371/journal.pone.0083580 http://hdl.handle.net/10481/30300 eng info:eu-repo/semantics/openAccess Public Library of Science (PLOS)