Characterization of the subtypes of cell motility in ageing human skin fibroblasts

Pienta, Kenneth J.; Coffey, Donald S.

doi:10.1016/0047-6374(90)90001-v

Cited by 50 publications

(24 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Molecular mass labels indicate marker position in the 10% gels. effect of aging on ®broblast migration in both chemotactic and chemokinetic assays (Albini et al, 1988;Pienta and Coffey, 1990) and are particularly relevant to the impact of hypoxia on wound healing since the aged experience a greater incidence of nonhealing wounds associated with low tissue O 2 supply (Eaglstein, 1989;Eaglstein and Falanga, 1997).…”

Section: Discussionmentioning

confidence: 99%

Effect of age and hypoxia on TGFβ1 receptor expression and signal transduction in human dermal fibroblasts: Impact on cell migration

Mogford

Tawil²,

Chen

et al. 2002

Journal Cellular Physiology

View full text Add to dashboard Cite

Wound healing is critically affected by age, ischemia, and growth factors such as TGFbeta1. The combined effect of these factors on fibroblast migration, an essential component of wound healing, is poorly understood. To address this deficiency, we examined expression of TGFbeta receptor type I and II (TGFbetaRI and RII) under normoxia or hypoxia (1% O(2)) in cultured human dermal fibroblasts (HDFs) from young (ages 24-33) and aged (ages 61-73) adults. TGFbetaRI and RII expression was similar in both groups under normoxia. Hypoxia did not alter receptor levels in young HDFs but significantly decreased TGFbetaRI in aged cells (12 and 43%, respectively). Additionally, young cells displayed a 50% increase in activation of p42/p44 mitogen-activated kinase by TGFbeta1 (2-200 pg/ml) under hypoxia while aged cell levels of active p42/p44 decreased up to 24%. To determine functional outcomes of these findings, we measured the migratory capacity of the cells on type I collagen using a gold salt migration assay. Hypoxia increased the migratory index (MI) of young HDFs over normoxia by 30% but had no effect on aged cells. Under normoxia, TGFbeta1 (1-1000 pg/ml) increased young HDF migration in a concentration-dependent manner up to 109% over controls but minimally increased aged HDF migration (37%). Under hypoxia, TGFbeta1 significantly increased young cell MI at all concentrations but was without effect on the aged HDF response. These data demonstrate that aged fibroblasts have an impaired migratory capacity with complete loss of responsiveness to hypoxia and deficits in the migratory and signal transduction responsiveness to TGFbeta1 that may partly explain diminished healing capabilities often observed in aged patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of age and hypoxia on TGFβ1 receptor expression and signal transduction in human dermal fibroblasts: Impact on cell migration

Mogford

Tawil²,

Chen

et al. 2002

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…Age-related diminution in non-stimulated dermal fibroblast motility has been attributed to global cell changes (23,39,40) and would thus be independent from the loss of EGF responsiveness noted in near senescent cells. This fits with our findings on early passage fibroblasts from aged donors; basal motility decreases, whereas EGF responsiveness is retained despite declining levels of EGFR.…”

Section: Discussionmentioning

confidence: 99%

Aging Fibroblasts Present Reduced Epidermal Growth Factor (EGF) Responsiveness Due to Preferential Loss of EGF Receptors

Shiraha¹,

Gupta²,

Drabik³

et al. 2000

Journal of Biological Chemistry

112

View full text Add to dashboard Cite

Wound healing is compromised in aging adults in part due to decreased responsiveness of fibroblasts to extracellular signals. However, the cellular mechanisms underlying this phenomenon are not known. Aged dermal fibroblasts with reduced remaining replicative capacities demonstrated decreased epidermal growth factor (EGF)-induced cell migrative and cell proliferative capacities, as reported previously. Thus, as cells approach senescence, programmed in vivo or in vitro, EGF responsiveness is preferentially lost. To define the rate-limiting signaling event, we found that the activity of two different EGF receptor (EGFR)-signaling pathways to cell migration (phospholipase-C ␥) and/or mitogenesis (extracellular signal/regulated-mitogen-activated kinases) were decreased in near senescent cells despite unchanged levels of effector molecules. Aged cells presented decreased levels of EGFR, although insulin receptor and transferrin receptor levels were relatively unchanged. EGFR mRNA levels and production of new transcripts decreased during aging, suggesting that this preferential loss of EGFR was due to diminished production, which more than counteracts the reduced ligand-induced receptor loss. Since these data suggested that the decrement in EGF was rate-limiting, higher levels of EGFR were established in near senescent cells by electroporation of EGFR cDNA. These cells presented higher levels of EGFR and recovered their EGF-induced migration and proliferation responsiveness. Thus, the defect in EGF responsiveness of aged dermal fibroblasts is secondary to reduced EGFR message transcription. Our experimental model suggests that EGFR gene delivery might be an effective future therapy for compromised wound healing.

show abstract

“…This relationship is progressive in rodent fibroblasts up to 12 mo of age, then plateaus and correlates directly with a reduction in healing of the donor site. In addition, motility of human fibroblasts in culture decreases with age of the donor and is independent of chemotactic gradients (41 ). Others have demonstrated that cytoskeletal (42) as well as genomic changes (43) …”

Section: Discussionmentioning

confidence: 99%

One systemic administration of transforming growth factor-beta 1 reverses age- or glucocorticoid-impaired wound healing.

Beck¹,

Deguzman²,

Lee³

et al. 1993

J. Clin. Invest.

226

109

View full text Add to dashboard Cite

show abstract

Characterization of the subtypes of cell motility in ageing human skin fibroblasts

Cited by 50 publications

References 17 publications

Effect of age and hypoxia on TGFβ1 receptor expression and signal transduction in human dermal fibroblasts: Impact on cell migration

Effect of age and hypoxia on TGFβ1 receptor expression and signal transduction in human dermal fibroblasts: Impact on cell migration

Aging Fibroblasts Present Reduced Epidermal Growth Factor (EGF) Responsiveness Due to Preferential Loss of EGF Receptors

One systemic administration of transforming growth factor-beta 1 reverses age- or glucocorticoid-impaired wound healing.

Contact Info

Product

Resources

About