Dlk1 up-regulates Gli1 expression in male rat adrenal capsule cells through the activation of β1 integrin and ERK1/2.
The development and maintenance of the zones of the adrenal cortex and their steroidal output are extremely important in the control of gluconeogenesis, the stress response, and blood volume. Sonic Hedgehog (Shh) is expressed in the adrenal cortex and signals to capsular cells, which can respond by migrating into the cortex and converting into a steroidogenic phenotype. Delta-like homologue 1 (Dlk1), a member of the Notch/Delta/Serrate family of epidermal growth factor-like repeat-containing proteins, has a well-established role in inhibiting adipocyte differentiation. We demonstrate that Shh and Dlk1 are coexpressed in the outer undifferentiated zone of the male rat adrenal and that Dlk1 signals to the adrenal capsule, activating glioma-associated oncogene homolog 1 transcription in a β1 integrin- and Erk1/2-dependent fashion. Moreover, Shh and Dlk1 expression inversely correlates with the size of the zona glomerulosa in rats after manipulation of the renin-angiotensin system, suggesting a role in the homeostatic maintenance of the gland.
Centre for Endocrinology, William Harvey Research Institute, Barts and the London, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom. p.j.king@qmul.ac.uk.
Leonardo
L
Guasti
Dominic
D
Cavlan
Kathryn
K
Cogger
Zahida
Z
Banu
Amreen
A
Shakur
Salima
S
Latif
Peter J
PJ
King
D000311:Adrenal Glands / Q000166:cytology*; D000818:Animals; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D000071676:Zinc Finger Protein GLI1
C512923:Dlk1 protein, rat; C498521:Gli1 protein, rat; D053823:Hedgehog Proteins; D019012:Integrin beta1; D036341:Intercellular Signaling Peptides and Proteins; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins; D012333:RNA, Messenger; C546888:Shh protein, rat; D000071676:Zinc Finger Protein GLI1; D048049:Extracellular Signal-Regulated MAP Kinases