TY - JOUR
T1 - The Parathyroid Hormone Second Receptor PTH2R and its Ligand Tuberoinfundibular Peptide of 39 Residues TIP39 Regulate Intracellular Calcium and Influence Keratinocyte Differentiation
AU - Sato, Emi
AU - Muto, Jun
AU - Zhang, Ling Juan
AU - Adase, Christopher A.
AU - Sanford, James A.
AU - Takahashi, Toshiya
AU - Nakatsuji, Teruaki
AU - Usdin, Ted B.
AU - Gallo, Richard L.
N1 - Funding Information:
This work was supported in part by NIH grants R01AI116576, R01AR064781, R01AI052453, R21AR0675478, U19AI117673, and P01HL107150 (RLG) and the UCSD Dermatologist Investigator Training Program T32AR062496 (JAS, CA).
Publisher Copyright:
© 2016 The Authors
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jid.2016.02.814
DO - 10.1016/j.jid.2016.02.814
M3 - Article
C2 - 27000502
AN - SCOPUS:84992488210
SN - 0022-202X
VL - 136
SP - 1449
EP - 1459
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 7
ER -