Isakson, B. E., Olsen, C. E., & Boitano, S. (2006). Laminin-332 alters connexin profile, dye coupling and intercellular Ca2+ waves in ciliated tracheal epithelial cells. Respiratory research, 7, 105.
Tracheal epithelial cells are anchored to a dynamic basement membrane that contains a variety of extracellular matrix proteins including collagens and laminins. During development, wound repair and disease of the airway epithelium, significant changes in extracellular matrix proteins may directly affect cell migration, differentiation and events mediated by intercellular communication. We hypothesized that alterations in cell matrix, specifically type I collagen and laminin alpha3beta3gamma2 (LM-332) proteins within the matrix, directly affect intercellular communication in ciliated rabbit tracheal epithelial cells (RTEC).
Lantz, R. C., Chau, B., & Boitano, S. A. (2016). Inhalation of arsenic-containing dusts during lung development alters pulmonary function in adult mice. Toxicological Sciences.
BIO5 Collaborators
Scott A Boitano, Clark Lantz
Tillu, D. V., Hassler, S. N., Burgos-Vega, C. C., Quinn, T. L., Sorge, R. E., Dussor, G., Boitano, S., Vagner, J., & Price, T. J. (2015). Protease activated receptor 2 (PAR2) activation is sufficient to induce the transition to a chronic pain state. Pain.
Protease Activated Receptor Type 2 (PAR2) is known to play an important role in inflammatory, visceral and cancer-evoked pain based on studies using PAR2 knockout (PAR2) mice. Here we have tested the hypothesis that specific activation of PAR2 is sufficient to induce a chronic pain state via extracellular signal-regulated kinase (ERK) signaling to protein synthesis machinery. We have further tested whether the maintenance of this chronic pain state involves a brain-derived neurotrophic factor (BDNF) / tropomyosin related kinase B (trkB) / atypical protein kinase C (aPKC) signaling axis. We observed that intraplantar injection of the novel, highly specific PAR2 agonist, 2-aminothiazol-4-yl-LIGRL-NH2 (2-at), evokes a long-lasting acute mechanical hypersensitivity (ED50 ∼ 12 pmoles), facial grimacing and causes robust hyperalgesic priming as revealed by a subsequent mechanical hypersensitivity and facial grimacing to prostaglandin E2 (PGE2) injection. The pro-mechanical hypersensitivity effect of 2-at is completely absent in PAR2 mice as is hyperalgesic priming. Intraplantar injection of the upstream ERK inhibitor, U0126 and the eukaryotic initiation factor (eIF) 4F complex inhibitor, 4EGI-1, prevented the development of acute mechanical hypersensitivity and hyperalgesic priming following 2-at injection. Systemic injection of the trkB antagonist ANA-12 likewise inhibited PAR2-mediated mechanical hypersensitivity, grimacing and hyperalgesic priming. Inhibition of aPKC (intrathecal delivery of ZIP) or trkB (systemic administration of ANA-12) after the resolution of 2-at-induced mechanical hypersensitivity reversed the maintenance of hyperalgesic priming. Hence, PAR2 activation is sufficient to induce neuronal plasticity leading to a chronic pain state, the maintenance of which is dependent on a BDNF/trkB/aPKC signaling axis.
Straub, A. C., Johnstone, S. R., Heberlein, K. R., Rizzo, M. J., Best, A. K., Boitano, S., & Isakson, B. E. (2010). Site-specific connexin phosphorylation is associated with reduced heterocellular communication between smooth muscle and endothelium. Journal of vascular research, 47(4), 277-86.
Myoendothelial junctions (MEJs) represent a specialized signaling domain between vascular smooth muscle cells (VSMC) and endothelial cells (EC). The functional consequences of phosphorylation state of the connexins (Cx) at the MEJ have not been explored.
Hassler, S., Boitano, S. A., Vagner, J., Price, T. J., & Dussor, G. (2017). Protease activated receptor 2 (PAR2) activation casues migraine-like pain behaviors in mice. Cephalalgia, In Revision.
