PTH-1R responses to PTHrP and regulation by vitamin D in keratinocytes and adjacent fibroblasts.
Vitamin D and PTHrP are essential for the differentiation of keratinocytes and epidermal development. The action of PTHrP on skin is mediated via its PTH-1R receptors present in both epidermal and dermal cells. This suggests that PTHrP may have a paracrine/autocrine role, and its receptors may act in association or in negative cooperativity. We compared the intracellular signaling pathways in response to PTHrP (1-34) and to various PTHrP peptides, the N-terminal (1-34), Mid region (67-89), and C-terminal (107-139) fragments, and the possible modulation of PTHrP and its receptor mRNA expressions by vitamin D. Adjacent dermal fibroblasts as freshly isolated keratinocytes expressed both PTHrP and PTH-1R mRNAs, and responded to the various PTHrP fragments. bPTH and PTHrP(1-34) increased both cellular cAMP and [Ca(2+)]i in keratinocytes and fibroblasts. In contrast, PTHrP (107-139) increased [Ca(2+)]i but not cAMP in the two cell types. PTHrP (67-89) had no effect in keratinocytes, and only increased [Ca(2+)]i in fibroblasts. Vitamin D deficiency in weaned rats increased the expression of PTHrP mRNA in keratinocytes, and decreased it in fibroblasts and kidneys. Vitamin D deficiency increased PTH-1R mRNA expression in keratinocytes and kidneys, but not in fibroblasts. Although keratinocytes and skin fibroblasts are target cells for PTHrP and express PTH-1R, the two adjacent cell types differ as regards their intracellular signaling in response to PTHrP peptides. Moreover vitamin D regulates PTHrP and PTH-1R in a cell-specific manner.
Errazahi
Amina
A
Centre National de la Recherche Scientifique CNRS UMR 8104-Institut National de la Recherche Médicale INSERM U567, Hôpital Saint Vincent de Paul, Bât ced, 82 Boulevard Denfert Rochereau, 75014 Paris, France.
Lieberherr
Michèle
M
Bouizar
Zhor
Z
Rizk-Rabin
Marthe
M
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics / Q000502:physiology*; D014807:Vitamin D / Q000494:pharmacology*
D044162:Parathyroid Hormone-Related Protein; D044168:Receptor, Parathyroid Hormone, Type 1; D014807:Vitamin D; D002118:Calcium