title: The Parathyroid Hormone Second Receptor PTH2R and its Ligand Tuberoinfundibular Peptide of 39 Residues TIP39 Regulate Intracellular Calcium and Influence Keratinocyte Differentiation.
abstract: Genes related to the parathyroid hormone (PTH) influence cutaneous immune defense and development, but the full functions of the PTH family in cutaneous biology remain incompletely understood. In this study, we examined the expression and potential functions of the PTH second receptor (PTH2R) and its ligand, the tuberoinfundibular peptide of 39 residues (TIP39), in the skin. TIP39 and PTH2R mRNA and protein were detectable in both human and mouse skin, and in cultured keratinocytes and adipocytes. TIP39 was observed in the basal layer of human skin, whereas PTH2R was detected in the spinous to granular layer. The subcellular localization of TIP39 in keratinocytes changed during calcium-induced differentiation and shifted to colocalize with PTH2R at the membrane. The addition of recombinant TIP39 to normal human keratinocytes in culture induced an increase in intercellular calcium and triggered aspects of terminal differentiation including decreased keratin-14 and increased involucrin expression. Consistent with these observations, PTH2R(-/-) mice were observed to have increased epidermal thickness. In summary, identification of TIP39 and its receptor in the epidermis reveals an additional PTH family member that is expressed in the skin and may influence keratinocyte function.
authors.affiliation: Department of Dermatology, University of California San Diego, La Jolla, California, USA.
authors.forename: Emi
authors.initials: E
authors.lastname: Sato
authors.affiliation: Department of Dermatology, Aichi Medical University, Nagakute, Aichi, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Muto
authors.affiliation: Department of Dermatology, University of California San Diego, La Jolla, California, USA.
authors.forename: Ling-Juan
authors.initials: LJ
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, University of California San Diego, La Jolla, California, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Adase
authors.affiliation: Department of Dermatology, University of California San Diego, La Jolla, California, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Sanford
authors.affiliation: Department of Dermatology, University of California San Diego, La Jolla, California, USA.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Dermatology, University of California San Diego, La Jolla, California, USA.
authors.forename: Teruaki
authors.initials: T
authors.lastname: Nakatsuji
authors.affiliation: Section on Fundamental Neuroscience, NIMH National Institute of Mental Health, Bethesda, Maryland, USA.
authors.forename: Ted B
authors.initials: TB
authors.lastname: Usdin
authors.affiliation: Department of Dermatology, University of California San Diego, La Jolla, California, USA. Electronic address: rgallo@ucsd.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation; D004721:Endoplasmic Reticulum; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D053547:Keratin-14 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009479:Neuropeptides / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D044183:Receptor, Parathyroid Hormone, Type 2 / Q000378:metabolism*; D012867:Skin / Q000378:metabolism
chemical_list: D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D053547:Keratin-14; C507446:Krt14 protein, mouse; D009479:Neuropeptides; D011498:Protein Precursors; D012333:RNA, Messenger; D044183:Receptor, Parathyroid Hormone, Type 2; C400136:tuberoinfundibular peptide 39; C032253:involucrin; D002118:Calcium