Abstract
Purpose:
Sjögren’s syndrome is a systemic chronic autoimmune inflammatory disease that targets primarily the salivary and lacrimal glands (LG). Recent data indicates that pannexin hemichannels are involved in signaling events leading to inflammation and cell death. At the same time Panx1 is implicated in healing process since it facilitates progenitor cell proliferation and differentiation during tissue regeneration. No specific role for Panx1 and other pannexins has been defined in the LG.
Methods:
Gene expression in murine LG was examined by qRT-PCR and immunostaining. Panx1 blocking peptide or saline (control) were co-administrated together with IL-1α injection. FACS isolated epithelial progenitors were used in transplantation experiments. Comparison of Panx1-null and WT LG morphology was performed using sections analysis.
Results:
Panx1 and 2 isoforms were expressed in the epithelial component of the LG; Panx2 labeling was also detectable in the blood vessels. Panx1 expression was also studied in the IL-1α injured LGs. IL-1α induces a strong immune response, extensive inflammation, and LG damage, followed by a regenerative phase. Panx1 was strongly induced during acute phase of LG inflammation and regeneration, peaking at 3 days and declining to the baseline level during 7 to 21 days post injury. Analysis of epithelial progenitor cells transplantation into IL-1α injured LG showed that efficiency of progenitor cell engraftment varied, depending on timing of cell injection. The lowest efficiency (1.43 ± 0.07%) of cell engraftment was found at one day after the injury, during acute LG inflammation. To test whether manipulation of Panx1 expression/function during injury-induced inflammation affects cell engraftment; we blocked Panx1 expression during LG inflammation phase. This manipulation increased engraftment of donor progenitor cells by approximately 63% relative to control. Genetic ablation of the Panx1 gene affected overall LG morphology and caused significant LG size reduction in Panx1-null mice, suggesting a specific role for Panx1 in LG morphogenesis. These data suggest that Panx1 mediated signaling may play distinct roles during different phases of LG inflammation and development/regeneration.
Conclusions:
Panx1 hemichanells are implicated in IL1-induced LG inflammatory injury and also may play a distinct role in LG morphogenesis and regeneration.
Keywords: 576 lacrimal gland •
447 cell-cell communication •
721 stem cells