Ephrin-A3 not only increases the density of hair follicles but also accelerates anagen development in neonatal mice

Yamada, Yuko; Midorikawa, Tatsuyuki; Oura, Hajimu; Yoshino, Teruhiko; Ohdera, Motoyasu; Kubo, Yoshiaki; Arase, Seiji

doi:10.1016/j.jdermsci.2008.05.007

Cited by 15 publications

(19 citation statements)

References 19 publications

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“…Ephrin-A3 and ephrin-B2 are also found in the dermal papilla, a fibroblast-enriched stromal region important for hair follicle cycling events. [132][133][134][135] Increased ephrin-A mRNA transcripts in mouse skin correlated with the onset of anagen with ephrin-A3 exhibiting the highest expression during this active growth phase. 135 The regulated expression of Eph receptors and ephrins in hair follicles and other skin appendages (i.e.…”

Section: Eph Receptors and Ephrins In Skinmentioning

confidence: 99%

“…[132][133][134][135] Increased ephrin-A mRNA transcripts in mouse skin correlated with the onset of anagen with ephrin-A3 exhibiting the highest expression during this active growth phase. 135 The regulated expression of Eph receptors and ephrins in hair follicles and other skin appendages (i.e. sebaceous glands, sweat glands) may play a role in determining cell fate and positioning during the hair cycle or epidermal wound repair, but this remains to be rigorously investigated.…”

Section: Eph Receptors and Ephrins In Skinmentioning

confidence: 99%

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Eph receptor and ephrin function in breast, gut, and skin epithelia

White¹,

Getsios

2014

Cell Adhesion & Migration

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Abbreviations: ADAM, a disintegrin and metalloprotease; Apc, adenomatous polyposis coli; Eph, erythropoietin-producing hepatocellular; ER, estrogen receptor; Erk, extracellular signal-regulated kinase; GEF, guanine nucleotide exchange factor; GPI, glycosylphosphatidylinositol; HER2, human epidermal growth factor receptor 2; HGF, hepatocyte growth factor; IBD, inflammatory bowel disease; KLF, Kr€ uppel-like factor; MAPK, mitogen-activated protein kinase; MMTV-LTR, mouse mammary tumor virus-long terminal repeat; MT1-MMP, membrane-type 1 matrix metalloproteinase; PDZ, postsynaptic density protein 95, discs large 1, and zonula occludens-1; PTP, protein tyrosine phosphatase; RTK, receptor tyrosine kinase; SH2, Src homology 2; SHIP2, SH2 inositol phosphatase 2; SLAP, Src-like adaptor protein; TCF, T-cell specific transcription factor; TEB, terminal end bud; TNFa, tumor necrosis factor a:Epithelial cells are tightly coupled together through specialized intercellular junctions, including adherens junctions, desmosomes, tight junctions, and gap junctions. A growing body of evidence suggests epithelial cells also directly exchange information at cell-cell contacts via the Eph family of receptor tyrosine kinases and their membrane-associated ephrin ligands. Ligand-dependent and -independent signaling via Eph receptors as well as reverse signaling through ephrins impact epithelial tissue homeostasis by organizing stem cell compartments and regulating cell proliferation, migration, adhesion, differentiation, and survival. This review focuses on breast, gut, and skin epithelia as representative examples for how Eph receptors and ephrins modulate diverse epithelial cell responses in a context-dependent manner. Abnormal Eph receptor and ephrin signaling is implicated in a variety of epithelial diseases raising the intriguing possibility that this cellcell communication pathway can be therapeutically harnessed to normalize epithelial function in pathological settings like cancer or chronic inflammation.

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Section: Eph Receptors and Ephrins In Skinmentioning

confidence: 99%

Section: Eph Receptors and Ephrins In Skinmentioning

confidence: 99%

Eph receptor and ephrin function in breast, gut, and skin epithelia

White¹,

Getsios

2014

Cell Adhesion & Migration

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“…For example, EphA1 has been found in all viable layers of the human epidermis but its expression is restricted to keratinocytes in the basal layer of mice [43,51]. Instead, EphA4 appears to be a major subtype present in the suprabasal layers of the mouse epidermis [14,18,49,52]. Interestingly, EphA4 not only has a high affinity for ephrin-A ligands but can also signal in response to ephrin-B2 [27,53,54].…”

Section: The Epidermal Eph/ephrin Axismentioning

confidence: 99%

Eph/ephrin signaling in epidermal differentiation and disease

Lin

Wang

Getsios

2012

Seminars in Cell & Developmental Biology

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Eph receptor tyrosine kinases mediate cell–cell communication by interacting with ephrin ligands residing on adjacent cell surfaces. In doing so, these juxtamembrane signaling complexes provide important contextual information about the cellular microenvironment that helps orchestrate tissue morphogenesis and maintain homeostasis. Eph/ephrin signaling has been implicated in various aspects of mammalian skin physiology, with several members of this large family of receptor tyrosine kinases and their ligands present in the epidermis, hair follicles, sebaceous glands, and underlying dermis. This review focuses on the emerging role of Eph receptors and ephrins in epidermal keratinocytes where they can modulate proliferation, migration, differentiation, and death. The activation of Eph receptors by ephrins at sites of cell–cell contact also appears to play a key role in the maturation of intercellular junctional complexes as keratinocytes move out of the basal layer and differentiate in the suprabasal layers of this stratified, squamous epithelium. Furthermore, alterations in the epidermal Eph/ephrin axis have been associated with cutaneous malignancy, wound healing defects and inflammatory skin conditions. These collective observations suggest that the Eph/ephrin cell–cell communication pathway may be amenable to therapeutic intervention for the purpose of restoring epidermal tissue homeostasis and integrity in dermatological disorders.

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“…The expression of a large number of ephrins and Eph receptors of both classes, with members of the same class often having redundant functions, together with the transient role for some ephrins in skin development [25,26] makes it difficult to study the role of ephrins and Ephs in mutant mice. We therefore instead decided to acutely inhibit the ephrin-Eph interaction.…”

Section: Proliferation In Telogen Follicles Is Regulated By Ephrins Amentioning

confidence: 99%

“…Not much is known about the Eph receptors and their ligands in skin, although several members have been localized to the follicular bulge region [24]. There are studies suggesting that Eph receptors and their ligands do have a transient role in regulating proliferation in both epidermis and hair follicles of neonatal mice [25,26]. Furthermore, in vitro studies have shown that ephrin-A3 increases proliferation in cultured outer root sheath cells from patients suffering from androgenic alopecia [27].…”

Section: Introductionmentioning

confidence: 99%

Ephrins Negatively Regulate Cell Proliferation in the Epidermis and Hair Follicle

2010

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Ephrins and their Eph tyrosine kinase receptors control many processes during embryonic development. They have more recently also been identified as important regulators of proliferation of stem/progenitor cells in the adult brain and intestine and have been implicated in tumorigenesis in a large number of tissues. We here describe the expression of a large number of ephrins and Eph receptors in the adult mouse skin. Disruption of the ephrin-Eph interaction in vivo with antagonists against the A or B class resulted in an approximate doubling of cell proliferation in the hair follicle and epidermis of adult mice. We conclude that ephrins are negative regulators of proliferation in the skin and that blocking the ephrin-Eph interaction may be an attractive strategy for regenerative therapies.

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Ephrin-A3 not only increases the density of hair follicles but also accelerates anagen development in neonatal mice

Cited by 15 publications

References 19 publications

Eph receptor and ephrin function in breast, gut, and skin epithelia

Eph receptor and ephrin function in breast, gut, and skin epithelia

Eph/ephrin signaling in epidermal differentiation and disease

Ephrins Negatively Regulate Cell Proliferation in the Epidermis and Hair Follicle

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