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Dong-Jin Oh, Guadalupe Villarreal, Jr., Min Hyung Kang, Douglas J. Rhee; Lithium Chloride Induces MicroRNA-29b and Suppresses Extracellular Matrix Synthesis in the Trabecular Meshwork. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3228.
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Recent work has suggested a growing importance for the microRNA-29 (miR-29) family in the regulation of extracellular matrix (ECM) synthesis in the trabecular meshwork (TM). In this study, we investigate the effects of lithium chloride (LiCl), a known activator of beta-catenin signaling, on miR-29 family expression and ECM synthesis in the TM.
Primary human TM cells were serum starved for 18 h and subsequently incubated for an additional 24 h in serum-free media containing 20 mM LiCl or sodium chloride (NaCl) vehicle. Changes in ECM synthesis were assessed via immunoblot analysis of conditioned media. Quantitative real-time PCR was used to determine the effects of LiCl or NaCl treatment on miR-29 family expression. Immunofluorescence was used to assess for nuclear translocation of beta-catenin.
LiCl treatment increased nuclear translocation of beta-catenin. Incubation of TM cells with LiCl resulted in a significant reduction in ECM protein synthesis compared to NaCl treatment. Levels of secreted protein acidic and rich in cysteine (SPARC), thrombospondin-1, collagen I, collagen IV, and laminin were reduced by 59%, 55%, 92%, 77%, and 81% respectively (n=4; p<0.001). Of note, LiCl treatment induced the expression of miR-29a by 22% (n=9; p=0.25), miR-29b by 57% (n=9; p=0.02), and miR-29c by 19% (n=9; p=0.33).
The findings derived from this study identify lithium chloride as an important regulator of miR-29b and ECM expression in the TM, and further suggest that miR-29b may function as a critical node in the modulation of ECM synthesis in the TM.
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