Human hair follicles are an extrarenal source and a nonhematopoietic target of erythropoietin

E. Bódó, Arno Kromminga, Wolfgang Funk, Magdalena Laugsch, Ute Duske, Wolfgang Jelkmann, Ralf Paus

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Erythropoietin primarily serves as an essential growth factor for erythrocyte precursor cells. However, there is increasing evidence that erythropoietin (EPO)/EPO receptor (EPO-R) signaling operates as a potential tissue-protective system outside the bone marrow. Arguing that growing hair follicles (HF) are among the most rapidly proliferating tissues, we have here explored whether human HFs are sources of EPO and targets of EPO-R-mediated signaling. Human scalp skin and microdissected HFs were assessed for EPO and EPO-R expression, and the effects of EPO on organ-cultured HFs were assessed in the presence/absence of a classical apoptosis-inducing chemotherapeutic agent. Here, we show that human scalp HFs express EPO on the mRNA and protein level in situ, up-regulate EPO transcription under hypoxic conditions, and express transcripts for EPO-R and the EPO-stimulatory transcriptional cofactor hypoxia-inducible factor-1α. Although EPO does not significantly alter human hair growth in vitro, it significantly down-regulates chemotherapy-induced intrafollicular apoptosis and changes the gene expression program of the HFs. The current study points to intriguing targets of EPO beyond the erythropoietic system: human HFs are an extrarenal site of EPO production and an extrahematopoietic site of EPO-R expression. They may recruit EPO/EPO-R signaling e.g., for modulating HF apoptosis under conditions of hypoxia and chemotherapy-induced stress.

Original languageEnglish
Pages (from-to)3346-3354
Number of pages9
JournalFASEB Journal
Volume21
Issue number12
DOIs
Publication statusPublished - Oct 2007

Fingerprint

erythropoietin
hair follicles
Hair Follicle
Erythropoietin
Chemotherapy
apoptosis
Apoptosis
Scalp
drug therapy
Tissue
Erythropoietin Receptors
Hypoxia-Inducible Factor 1
Drug Therapy

Keywords

  • Aminase oxidase
  • Anagen hair follicles
  • Calmegin
  • Hemoglobin alpha-1
  • Kinesin light chain 3
  • RAS-like family 10
  • Tissue protection

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology
  • Medicine(all)

Cite this

Bódó, E., Kromminga, A., Funk, W., Laugsch, M., Duske, U., Jelkmann, W., & Paus, R. (2007). Human hair follicles are an extrarenal source and a nonhematopoietic target of erythropoietin. FASEB Journal, 21(12), 3346-3354. https://doi.org/10.1096/fj.07-8628com

Human hair follicles are an extrarenal source and a nonhematopoietic target of erythropoietin. / Bódó, E.; Kromminga, Arno; Funk, Wolfgang; Laugsch, Magdalena; Duske, Ute; Jelkmann, Wolfgang; Paus, Ralf.

In: FASEB Journal, Vol. 21, No. 12, 10.2007, p. 3346-3354.

Research output: Contribution to journalArticle

Bódó, E, Kromminga, A, Funk, W, Laugsch, M, Duske, U, Jelkmann, W & Paus, R 2007, 'Human hair follicles are an extrarenal source and a nonhematopoietic target of erythropoietin', FASEB Journal, vol. 21, no. 12, pp. 3346-3354. https://doi.org/10.1096/fj.07-8628com
Bódó, E. ; Kromminga, Arno ; Funk, Wolfgang ; Laugsch, Magdalena ; Duske, Ute ; Jelkmann, Wolfgang ; Paus, Ralf. / Human hair follicles are an extrarenal source and a nonhematopoietic target of erythropoietin. In: FASEB Journal. 2007 ; Vol. 21, No. 12. pp. 3346-3354.
@article{4b15b82b21ab466e9f3d27d2fd8a1318,
title = "Human hair follicles are an extrarenal source and a nonhematopoietic target of erythropoietin",
abstract = "Erythropoietin primarily serves as an essential growth factor for erythrocyte precursor cells. However, there is increasing evidence that erythropoietin (EPO)/EPO receptor (EPO-R) signaling operates as a potential tissue-protective system outside the bone marrow. Arguing that growing hair follicles (HF) are among the most rapidly proliferating tissues, we have here explored whether human HFs are sources of EPO and targets of EPO-R-mediated signaling. Human scalp skin and microdissected HFs were assessed for EPO and EPO-R expression, and the effects of EPO on organ-cultured HFs were assessed in the presence/absence of a classical apoptosis-inducing chemotherapeutic agent. Here, we show that human scalp HFs express EPO on the mRNA and protein level in situ, up-regulate EPO transcription under hypoxic conditions, and express transcripts for EPO-R and the EPO-stimulatory transcriptional cofactor hypoxia-inducible factor-1α. Although EPO does not significantly alter human hair growth in vitro, it significantly down-regulates chemotherapy-induced intrafollicular apoptosis and changes the gene expression program of the HFs. The current study points to intriguing targets of EPO beyond the erythropoietic system: human HFs are an extrarenal site of EPO production and an extrahematopoietic site of EPO-R expression. They may recruit EPO/EPO-R signaling e.g., for modulating HF apoptosis under conditions of hypoxia and chemotherapy-induced stress.",
keywords = "Aminase oxidase, Anagen hair follicles, Calmegin, Hemoglobin alpha-1, Kinesin light chain 3, RAS-like family 10, Tissue protection",
author = "E. B{\'o}d{\'o} and Arno Kromminga and Wolfgang Funk and Magdalena Laugsch and Ute Duske and Wolfgang Jelkmann and Ralf Paus",
year = "2007",
month = "10",
doi = "10.1096/fj.07-8628com",
language = "English",
volume = "21",
pages = "3346--3354",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "12",

}

TY - JOUR

T1 - Human hair follicles are an extrarenal source and a nonhematopoietic target of erythropoietin

AU - Bódó, E.

AU - Kromminga, Arno

AU - Funk, Wolfgang

AU - Laugsch, Magdalena

AU - Duske, Ute

AU - Jelkmann, Wolfgang

AU - Paus, Ralf

PY - 2007/10

Y1 - 2007/10

N2 - Erythropoietin primarily serves as an essential growth factor for erythrocyte precursor cells. However, there is increasing evidence that erythropoietin (EPO)/EPO receptor (EPO-R) signaling operates as a potential tissue-protective system outside the bone marrow. Arguing that growing hair follicles (HF) are among the most rapidly proliferating tissues, we have here explored whether human HFs are sources of EPO and targets of EPO-R-mediated signaling. Human scalp skin and microdissected HFs were assessed for EPO and EPO-R expression, and the effects of EPO on organ-cultured HFs were assessed in the presence/absence of a classical apoptosis-inducing chemotherapeutic agent. Here, we show that human scalp HFs express EPO on the mRNA and protein level in situ, up-regulate EPO transcription under hypoxic conditions, and express transcripts for EPO-R and the EPO-stimulatory transcriptional cofactor hypoxia-inducible factor-1α. Although EPO does not significantly alter human hair growth in vitro, it significantly down-regulates chemotherapy-induced intrafollicular apoptosis and changes the gene expression program of the HFs. The current study points to intriguing targets of EPO beyond the erythropoietic system: human HFs are an extrarenal site of EPO production and an extrahematopoietic site of EPO-R expression. They may recruit EPO/EPO-R signaling e.g., for modulating HF apoptosis under conditions of hypoxia and chemotherapy-induced stress.

AB - Erythropoietin primarily serves as an essential growth factor for erythrocyte precursor cells. However, there is increasing evidence that erythropoietin (EPO)/EPO receptor (EPO-R) signaling operates as a potential tissue-protective system outside the bone marrow. Arguing that growing hair follicles (HF) are among the most rapidly proliferating tissues, we have here explored whether human HFs are sources of EPO and targets of EPO-R-mediated signaling. Human scalp skin and microdissected HFs were assessed for EPO and EPO-R expression, and the effects of EPO on organ-cultured HFs were assessed in the presence/absence of a classical apoptosis-inducing chemotherapeutic agent. Here, we show that human scalp HFs express EPO on the mRNA and protein level in situ, up-regulate EPO transcription under hypoxic conditions, and express transcripts for EPO-R and the EPO-stimulatory transcriptional cofactor hypoxia-inducible factor-1α. Although EPO does not significantly alter human hair growth in vitro, it significantly down-regulates chemotherapy-induced intrafollicular apoptosis and changes the gene expression program of the HFs. The current study points to intriguing targets of EPO beyond the erythropoietic system: human HFs are an extrarenal site of EPO production and an extrahematopoietic site of EPO-R expression. They may recruit EPO/EPO-R signaling e.g., for modulating HF apoptosis under conditions of hypoxia and chemotherapy-induced stress.

KW - Aminase oxidase

KW - Anagen hair follicles

KW - Calmegin

KW - Hemoglobin alpha-1

KW - Kinesin light chain 3

KW - RAS-like family 10

KW - Tissue protection

UR - http://www.scopus.com/inward/record.url?scp=35248836135&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35248836135&partnerID=8YFLogxK

U2 - 10.1096/fj.07-8628com

DO - 10.1096/fj.07-8628com

M3 - Article

VL - 21

SP - 3346

EP - 3354

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 12

ER -