Epithelial Transport

Pflügers Archiv

, Volume 452, Issue 1, pp 43-52

First online:

Evidence that TRPC1 contributes to calcium-induced differentiation of human keratinocytes

  • Shiwei CaiAffiliated withDepartment of Oral Biology, University of Washington
  • , Sahba FatheraziAffiliated withDepartment of Oral Biology, University of Washington
  • , Richard B. PreslandAffiliated withDepartment of Oral Biology, University of WashingtonDivision of Dermatology, Department of Medicine, University of Washington
  • , Carol M. BeltonAffiliated withDepartment of Oral Biology, University of Washington
  • , Frank A. RobertsAffiliated withDepartment of Periodontics, University of Washington
  • , Paul C. GoodwinAffiliated withApplied Precision
  • , Mark M. SchubertAffiliated withDepartment of Oral Medicine, University of Washington
  • , Kenneth T. IzutsuAffiliated withDepartment of Oral Biology, University of Washington Email author 

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Abstract

External calcium ion concentration is a major regulator of epidermal keratinocyte differentiation in vitro and probably also in vivo. Regulation of calcium-induced differentiation changes is proposed to occur via an external calcium-sensing, signaling pathway that utilizes increases in intracellular calcium ion concentration to activate differentiation-related gene expression. Calcium ion release from intracellular stores and calcium ion influx via store-operated calcium-permeable channels are key elements in this proposed signaling pathway; however, the channels involved have not yet been identified. The present report shows that human gingival keratinocytes (HGKs) also undergo calcium-induced differentiation in vitro as indicated by involucrin expression and morphological changes. Moreover, TRPC1, which functions as a store-operated calcium channel in a number of cell types, including epidermal keratinocytes, is expressed in both proliferating and differentiating HGKs. Transfection of HGKs with TRPC1 siRNA disrupted expression of TRPC1 mRNA and protein compared with transfection with scrambled TRPC1 siRNA. Cells with disrupted TRPC1 expression showed decreased calcium-induced differentiation as measured by involucrin expression or morphological changes, as well as decreased thapsigargin-induced calcium ion influx, and a decreased rate of store calcium release. These results indicate that TRPC1 is involved in calcium-induced differentiation of HGKs likely by supporting a store-operated calcium ion influx.

Keywords

Differentiation Involucrin Gingiva TRPC Store-operated calcium influx