PMID- 19609315
OWN - NLM
STAT- MEDLINE
DCOM- 20100128
LR  - 20211020
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Print)
IS  - 0022-202X (Linking)
VI  - 130
IP  - 1
DP  - 2010 Jan
TI  - Metalloproteinase-mediated, context-dependent function of amphiregulin and HB-EGF 
      in human keratinocytes and skin.
PG  - 295-304
LID - 10.1038/jid.2009.211 [doi]
AB  - Human keratinocytes (KCs) express multiple EGF receptor (EGFR) ligands; however, 
      their functions in specific cellular contexts remain largely undefined. To 
      address this issue, first we measured mRNA and protein levels for multiple EGFR 
      ligands in KCs and skin. Amphiregulin (AREG) was by far the most abundant EGFR 
      ligand in cultured KCs, with >19 times more mRNA and >7.5 times more shed protein 
      than any other family member. EGFR ligand expression in normal skin was low (<8 
      per thousand of RPLP0/36B4); however, HB-EGF and AREG mRNAs were strongly induced 
      in human skin organ culture. KC migration in scratch wound assays was highly 
      metalloproteinase (MP)- and EGFR dependent, and was markedly inhibited by EGFR 
      ligand antibodies. However, lentivirus-mediated expression of soluble HB-EGF, but 
      not soluble AREG, strongly enhanced KC migration, even in the presence of MP 
      inhibitors. Lysophosphatidic acid (LPA)-induced ERK phosphorylation was also 
      strongly EGFR and MP dependent and markedly inhibited by neutralization of 
      HB-EGF. In contrast, autocrine KC proliferation and ERK phosphorylation were 
      selectively blocked by neutralization of AREG. These data show that distinct EGFR 
      ligands stimulate KC behavior in different cellular contexts, and in an 
      MP-dependent fashion.
FAU - Stoll, Stefan W
AU  - Stoll SW
AD  - Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, 
      USA. sstoll@umich.edu
FAU - Johnson, Jessica L
AU  - Johnson JL
FAU - Bhasin, Ajay
AU  - Bhasin A
FAU - Johnston, Andrew
AU  - Johnston A
FAU - Gudjonsson, Johann E
AU  - Gudjonsson JE
FAU - Rittie, Laure
AU  - Rittie L
FAU - Elder, James T
AU  - Elder JT
LA  - eng
GR  - K01 AR050462-03/AR/NIAMS NIH HHS/United States
GR  - R03 AR049420/AR/NIAMS NIH HHS/United States
GR  - R03 AR049420-03/AR/NIAMS NIH HHS/United States
GR  - K01 AR050462/AR/NIAMS NIH HHS/United States
GR  - R01 AR 052889/AR/NIAMS NIH HHS/United States
GR  - R01 AR052889/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (HBEGF protein, human)
RN  - 0 (Heparin-binding EGF-like Growth Factor)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Ligands)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.4.- (Metalloproteases)
SB  - IM
MH  - Amphiregulin
MH  - Autocrine Communication/physiology
MH  - Cell Division/physiology
MH  - Cell Movement/*physiology
MH  - Cells, Cultured
MH  - EGF Family of Proteins
MH  - ErbB Receptors/metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Glycoproteins/genetics/*metabolism
MH  - Heparin-binding EGF-like Growth Factor
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Keratinocytes/cytology/*metabolism
MH  - Lentivirus/genetics
MH  - Ligands
MH  - Lipopolysaccharides/pharmacology
MH  - Metalloproteases/antagonists & inhibitors/*metabolism
MH  - Organ Culture Techniques
MH  - Phosphorylation/drug effects/physiology
MH  - RNA, Messenger/metabolism
MH  - Signal Transduction/physiology
MH  - Skin/cytology
PMC - PMC2795126
MID - NIHMS134079
EDAT- 2009/07/18 09:00
MHDA- 2010/01/29 06:00
PMCR- 2011/01/01
CRDT- 2009/07/18 09:00
PHST- 2009/07/18 09:00 [entrez]
PHST- 2009/07/18 09:00 [pubmed]
PHST- 2010/01/29 06:00 [medline]
PHST- 2011/01/01 00:00 [pmc-release]
AID - S0022-202X(15)34551-6 [pii]
AID - 10.1038/jid.2009.211 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2010 Jan;130(1):295-304. doi: 10.1038/jid.2009.211.