Epidermal Growth Factor and Transforming Growth Factor-α

Nanney, Lillian B.; KingJr., Lloyd E.

doi:10.1007/978-1-4899-0185-9_5

Cited by 23 publications

(28 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A major wellcharacterized effect of TGF␣ on cells of the epidermal origin is enhancement of cell proliferation and migration, which often cannot occur simultaneously. In vivo studies showed that increased local concentrations of TGF␣ or overexpression of EGFR plays an important role in both physiological processes, such as wound healing and hair follicle development, and pathological disorders, such as psoriasis (hyperproliferation of keratinocytes) and skin tumorigenesis (15,32). However, ablation of TGF␣ or EGFR genes in mice only resulted in some visible abnormalities in the outer root sheath and hair follicle architecture, likely due to the multiple family members present at both the ligand and receptor levels of TGF␣ (27,28).…”

mentioning

confidence: 99%

Transforming Growth Factor α (TGFα)-Stimulated Secretion of HSP90α: Using the Receptor LRP-1/CD91 To Promote Human Skin Cell Migration against a TGFβ-Rich Environment during Wound Healing

Cheng¹,

Fan²,

Fedesco³

et al. 2008

Molecular and Cellular Biology

200

227

View full text Add to dashboard Cite

Jump-starting and subsequently maintaining epidermal and dermal cell migration are essential processes for skin wound healing. These events are often disrupted in nonhealing wounds, causing patient morbidity and even fatality. Currently available treatments are unsatisfactory. To identify novel wound-healing targets, we investigated secreted molecules from transforming growth factor ␣ (TGF␣)-stimulated human keratinoytes, which contained strong motogenic, but not mitogenic, activity. Protein purification allowed us to identify the heat shock protein 90␣ (hsp90␣) as the factor fully responsible for the motogenic activity in keratinocyte secretion. TGF␣ causes rapid membrane translocation and subsequent secretion of hsp90␣ via the unconventional exosome pathway in the cells. Secreted hsp90␣ promotes both epidermal and dermal cell migration through the surface receptor LRP-1 (LDL receptor-related protein 1)/CD91. The promotility activity resides in the middle domain plus the charged sequence of hsp90␣ but is independent of the ATPase activity. Neutralizing the extracellular function of hsp90␣ blocks TGF␣-induced keratinicyte migration. Most intriguingly, unlike the effects of canonical growth factors, the hsp90␣ signaling overrides the inhibition of TGF␤, an abundant inhibitor of dermal cell migration in skin wounds. This finding provides a long-sought answer to the question of how dermal cells migrate into the wound environment to build new connective tissues and blood vessels. Thus, secreted hsp90␣ is potentially a new agent for wound healing.

show abstract

mentioning

confidence: 99%

Transforming Growth Factor α (TGFα)-Stimulated Secretion of HSP90α: Using the Receptor LRP-1/CD91 To Promote Human Skin Cell Migration against a TGFβ-Rich Environment during Wound Healing

Cheng¹,

Fan²,

Fedesco³

et al. 2008

Molecular and Cellular Biology

200

227

View full text Add to dashboard Cite

show abstract

“…5 A). PD153035 treatment led to a pronounced (2)(3)(4)(5)(6) outgrowths from the same tissue fragment. Significance values determined for differences in average outgrowth area were as follows: day 2, P ϭ 0.63, n ϭ 2; day 3, P ϭ 0.13, n ϭ 3; day 4, P ϭ 0.10, n ϭ 3; day 6, P ϭ 0.005, n ϭ 3; day 8, P ϭ 0.006, n ϭ 2. reduction in outgrowth area, with marked differences in outgrowth size and morphology becoming evident by day 6.…”

Section: Production Of Hb-egf and Total Protein By Organ Cultures Is mentioning

confidence: 95%

“…Keratinocytes produce a number of growth factors, among which members of the EGF family are prominent: TGF-␣ , amphiregulin (AR), 1 and heparin-binding EGF-like growth factor (HB-EGF) (4,5). Epidermal growth factor receptor (EGFR) activation causes autoinduction of multiple EGF family members in keratinocytes (6-9) via a mechanism primarily involving mRNA stabilization (10,11).…”

Section: Introductionmentioning

confidence: 99%

Heparin-binding ligands mediate autocrine epidermal growth factor receptor activation In skin organ culture.

Stoll¹,

Garner²,

Elder³

1997

J. Clin. Invest.

103

122

View full text Add to dashboard Cite

Exogenous EGF and TGF-␣ accelerate wound healing, but treatment effects are often modest. Using short-term human skin organ culture, we found that autocrine EGF receptor activation could account for this observation. Amphiregulin and heparin-binding EGF-like growth factor (HB-EGF) transcripts were rapidly and markedly induced, whereas EGF and TGF-␣ mRNAs were undetectable or only slightly increased. Vascular permeability factor and keratin 6 transcripts were also strongly induced, albeit with a Ն 3 h delay relative to HB-EGF and amphiregulin. All four transcripts were upregulated in actual healing skin wounds, HB-EGF and keratin 6 being the most prominent. The highly EGF receptor-specific tyrosine kinase inhibitor PD153035 strongly inhibited induction of all four transcripts in organ culture, as well as release of immunoreactive HB-EGF into the medium. These effects were confirmed using the anti-EGF receptor mAb 225 IgG. Neither PD153035 nor 225 IgG was toxic to keratinocytes, as judged by calcein-AM uptake. PD153035 completely abrogated the proliferative phase of keratinocyte outgrowth in skin explant cultures, whereas it had no effect on the antecedent migratory phase. Based on these results, we conclude that EGF receptor activation by highly inducible, keratinocyte-derived heparin-binding ligands is an important mechanism for amplification and transmission of the cutaneous wound healing signal. ( J.

show abstract

“…It binds to the EGF receptor (EGFR) which is also a receptor for EGFrelated cytokines such as transforming growth factor α (TGFα) (Derynck, 1986). In normal adult epidermis, EGFR is predominantly expressed in basal keratinocytes and signalling events elicited by it are known to affect their proliferation, differentiation and migration (Vassar and Fuchs, 1991) (reviewed in Nanney and King, 1996). In healing skin wounds, EGFR expression is upregulated in migrating and proliferating keratinocytes adjacent to the wound (reviewed in Nanney and King, 1996).…”

Section: Introductionmentioning

confidence: 99%

“…In normal adult epidermis, EGFR is predominantly expressed in basal keratinocytes and signalling events elicited by it are known to affect their proliferation, differentiation and migration (Vassar and Fuchs, 1991) (reviewed in Nanney and King, 1996). In healing skin wounds, EGFR expression is upregulated in migrating and proliferating keratinocytes adjacent to the wound (reviewed in Nanney and King, 1996). Clinical studies of the influence of treatment of skin wounds with soluble EGF have revealed a stimulatory function of this growth factor in wound healing (Brown et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Regulation of keratinocyte shape, migration and wound epithelialization by IGF-1- and EGF-dependent signalling pathways

Haase

Evans

Pofahl

et al. 2003

Journal of Cell Science

215

193

View full text Add to dashboard Cite

Fig. 8. Effect of toxin B and ML-7 on wound epithelialization in vitro. Mitomycin-C-treated keratinocytes in FAD low Ca 2+ were wounded and incubated for 6 hours in the presence of growth factors. Wounded monolayers were stimulated with 100 ng ml -1 IGF-1 (A,B) or 10 ng ml -1 EGF (C-E) in the presence of 20 ng ml -1 toxin B (B) and 5 µM (D) or 10 µM (E) ML-7 or the respective vehicle controls (A,C).

show abstract

Epidermal Growth Factor and Transforming Growth Factor-α

Cited by 23 publications

References 108 publications

Transforming Growth Factor α (TGFα)-Stimulated Secretion of HSP90α: Using the Receptor LRP-1/CD91 To Promote Human Skin Cell Migration against a TGFβ-Rich Environment during Wound Healing

Transforming Growth Factor α (TGFα)-Stimulated Secretion of HSP90α: Using the Receptor LRP-1/CD91 To Promote Human Skin Cell Migration against a TGFβ-Rich Environment during Wound Healing

Heparin-binding ligands mediate autocrine epidermal growth factor receptor activation In skin organ culture.

Regulation of keratinocyte shape, migration and wound epithelialization by IGF-1- and EGF-dependent signalling pathways

Contact Info

Product

Resources

About