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Reports

Potassium-Chloride Cotransporter Mediates Cell Cycle Progression and Proliferation of Human Corneal Epithelial Cells

José E. Capó-Aponte, Zheng Wang, M.A. Murat Akinci, J. Mario Wolosin, Kathryn S. Pokorny, Pavel Iserovish and Peter S. Reinach

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Epidermal growth factor (EGF)-induced proliferation of corneal epithelial cells contributes to its renewal, which maintains the protective and refractive properties of the cornea. This study characterized in human corneal epithelial cells (HCEC) the role of the potassium–chloride cotransporter (KCC) in mediating (i) EGF-induced mitogen-activated protein kinase (MAPK) pathway activation; (ii) increases in cell cycle progression; and (iii) proliferation. The KCC inhibitor [(dihydroindenyl)oxy] alkanoic acid (DIOA) and KCC activator N-ethylmaleimide (NEM), suppressed and enhanced EGF-induced p44/42MAPK activation, respectively. Such selective modulation was mirrored by corresponding changes in cell proliferation and shifts in cell cycle distribution. DIOA induced a 20% increase in G0/G1-phase cell population, whereas NEM induced a 22% increase in the proportion of cells in the G2/M-phase and accelerated the transition from G0/G1-phase to the S-phase. Associated with these changes, KCC1 content in a plasma membrane enriched fraction increased by 300%. Alterations in regulatory volume capacity were associated with corresponding changes in both KCC1 membrane content and activity. These results indicate that EGF-induced increases in KCC1 activity and content modulate cell volume changes required for (i) activation of the p44/42MAPK signaling pathway, (ii) cell cycle progression, and (iii) increases in cell proliferation.

Authors

José E. Capó-Aponte

State University of New York; New York, NY

Zheng Wang

State University of New York; New York, NY

M.A. Murat Akinci

Mount Sinai School of Medicine; New York, NY

J. Mario Wolosin

Mount Sinai School of Medicine; New York, NY

Kathryn S. Pokorny

University of Medicine & Dentistry of New Jersey; Newark, NJ

Pavel Iserovish

Columbia University; New York, NY

Peter S. Reinach

State University of New York; New York, NY

Purchase article for $19

Subscribe to this journal for $129/year