title: Role of the calcium-sensing receptor in calcium regulation of epidermal differentiation and function.
abstract: The epidermis is a stratified squamous epithelium composed of proliferating basal and differentiated suprabasal keratinocytes. It serves as the body's major physical and chemical barrier against infection and harsh environmental insults, as well as preventing excess water loss from the body into the atmosphere. Calcium is a key regulator of the proliferation and differentiation in keratinocytes. Elevated extracellular Ca(2+) concentration ([Ca(2+)]o) raises the levels of intracellular free calcium ([Ca(2+)]i), promotes cell-cell adhesion, and activates differentiation-related genes. Keratinocytes deficient in the calcium-sensing receptor fail to respond to [Ca(2+)]o stimulation and to differentiate, indicating a role for the calcium-sensing receptor in transducing the [Ca(2+)]o signal during differentiation. The concepts derived from in vitro gene knockdown experiments have been evaluated and confirmed in three mouse models in vivo.
authors.affiliation: Endocrine Unit, Veterans Affair Medical Center and The University of California, San Francisco, CA, USA.
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Tu
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Bikle
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology; D044169:Receptors, Calcium-Sensing / Q000502:physiology*
chemical_list: D044169:Receptors, Calcium-Sensing; D002118:Calcium
keywords: E-cadherin; calcium-sensing receptor; intracellular free Ca(2+) (Ca(2+)(i)); keratinocyte differentiation; permeability barrier