Sortilin is expressed in cultured human keratinocytes and is regulated by cutaneous neuropeptides.
Sortilin, a member of the family of Vps10p domain receptors, has been shown to be able to bind the precursor peptide of nerve growth factor (proNGF). ProNGF interacts with sortilin and the p75(NTR) receptor on the cell surface to form a molecular complex capable of activating an apoptotic cascade. Keratinocytes can secrete proNGF and they have p75(NTR) on their surface. The expression of sortilin in normal human keratinocytes has not yet been clearly shown. In this study, we show that keratinocytes express sortilin mRNA, and the presence of sortilin protein is shown in cultured keratinocytes and in normal human skin. We have also shown that the cutaneous neuropeptides substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, and galanin are able to reduce the expression of sortilin mRNA and sortilin protein in cultured human keratinocytes. In addition, each of the analyzed neuropeptides has the ability to arrest the proNGF-induced apoptosis of human keratinocytes. These results suggest that all the participants in the NGF/proNGF pathway are present in the keratinocytes, and cutaneous neuropeptides can modulate their expressions and actions. The NGF/proNGF balance and its regulation by neuropeptides may have an important role in skin homeostasis.
Kiss
Mária
M
Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary. km@dermall.hu
Dallos
Attila
A
Kormos
Bernadett
B
Sántha
Petra
P
Dobozy
Attila
A
Husz
Sándor
S
Kemény
Lajos
L
D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D019004:Galanin / Q000378:metabolism / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology*; D011498:Protein Precursors / Q000378:metabolism / Q000494:pharmacology; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D012867:Skin / Q000166:cytology; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000494:pharmacology; D055815:Young Adult; D000099183:Sortilin
D033942:Adaptor Proteins, Vesicular Transport; D015740:Calcitonin Gene-Related Peptide; D019004:Galanin; D020932:Nerve Growth Factor; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D011498:Protein Precursors; D017475:Receptors, Nerve Growth Factor; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D000099183:Sortilin; C484065:NGFR protein, human; C061397:pro-nerve growth factor, human