Manipulation of Panx1 Activity Increases the Engraftment of Transplanted Lacrimal Gland Epithelial Progenitor Cells

Investigative Ophthalmology & Visual Science
Liana V BasovaHelen P Makarenkova

Abstract

Sjögren's syndrome is a systemic chronic autoimmune inflammatory disease that primarily targets the salivary and lacrimal glands (LGs). Currently there is no cure; therefore, cell-based regenerative therapy may be a viable option. LG inflammation is facilitated by extracellular ATP and mediated by the Pannexin-1 (Panx1) membrane channel glycoprotein. We propose that suppression of inflammation through manipulation of Panx1 activity can stimulate epithelial cell progenitor (EPCP) engraftment. The expression of pannexins in the mouse and human LG was assayed by qRT-PCR and immunostaining. Acute LG inflammation was induced by interleukin-1α (IL1α) injection. Prior to EPCP transplantation, IL1α-injured or chronically inflamed LGs of thrombospondin-1-null mice (TSP-1-/-) were treated with the Panx1-specific blocking peptide (10panx) or the self-deliverable RNAi (sdRNAi). The efficacy of cell engraftment and the area of inflammation were analyzed by microscopy. Panx1 and Panx2 were detected in the mouse and human LGs. Panx1 and proinflammatory factors were upregulated during acute inflammation at days 1 to 3 after the IL1α injection. The analysis of EPCP engraftment demonstrated a significant and reproducible positive correlation bet...Continue Reading

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Citations

Jun 28, 2019·Current Eye Research·Jana Dietrich, Stefan Schrader
May 22, 2018·Frontiers in Molecular Neuroscience·Paige Whyte-FagundesGeorg Zoidl
Jan 5, 2021·Molecular and Cellular Biochemistry·Eijaz Ahmed Bhat, Nasreena Sajjad

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Methods Mentioned

BETA
Fluorescence
fluorescence activated cell sorting
FACS
Flow Cytometry
PCR
SMA
transfection

Software Mentioned

Prism
GraphPad

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