Proton and electron microprobe analysis of human skin

Malmqvist, Klas; Carlsson, Lars-Eric; Forslind, B; Roomans, Godfried M.; Akselsson, K. Roland

doi:10.1016/0168-583x(84)90447-6

Cited by 62 publications

(26 citation statements)

References 8 publications

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“…However, this is the first report linking the insulininduced proliferation with PKC␦-mediated induction of the Na + /K + pump in keratinocytes. These results are in accordance with the existence of an ion gradient in skin in vivo and with the well-documented effects of Ca 2+ , K + , and Na + ions on keratinocyte proliferation and differentiation (52)(53)(54). These observations are consistent with a role for both insulin and the Na + /K + pump in keratinocyte proliferation and may explain the significance of insulin as an essential component of growth medium of cultured keratinocytes.…”

Section: Discussionsupporting

confidence: 74%

PKCδ Activation

et al. 2001

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Insulin and insulin-like growth factor-1 (IGF-1) are members of the family of the insulin family of growth factors, which activate similar cellular downstream pathways. In this study, we analyzed the effects of insulin and IGF-1 on the proliferation of murine skin keratinocytes in an attempt to determine whether these hormones trigger the same signaling pathways. Increasing doses of insulin and IGF-1 promote keratinocyte proliferation in an additive manner. We identified downstream pathways specifically involved in insulin signaling that are known to play a role in skin physiology; these include activation of the Na + /K + pump and protein kinase C (PKC). Insulin, but not IGF-1, stimulated Na + /K + pump activity. Furthermore, ouabain, a specific Na + /K + pump inhibitor, abolished the proliferative effect of insulin but not that of IGF-1. Insulin and IGF-1 also differentially regulated PKC activation. Insulin, but not IGF-1, specifically activated and translocated the PKC␦ isoform to the membrane fraction. There was no effect on PKC isoforms ␣, , , and , which are expressed in skin. PKC␦ overexpression increased keratinocyte proliferation and Na + /K + pump activity to a degree similar to that induced by insulin but had no affect on IGF-1-induced proliferation. Furthermore, a dominant negative form of PKC␦ abolished the effects of insulin on both proliferation and Na + /K + pump activity but did not abrogate induction of keratinocyte proliferation induced by other growth factors. These data indicate that though insulin or IGF-1 stimulation induce keratinocyte proliferation, only insulin action is specifically mediated via PKC␦ and involves activation of the Na + /K + pump. Diabetes 50:255-264, 2001

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Section: Discussionsupporting

confidence: 74%

PKCδ Activation

et al. 2001

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“…Calcium is a known regulator o f differentiation in a variety o f stratifying epithelial cell types, including epithelial cells derived from epidermis (Hennings et al, 1980;Rubin & Rice, 1986, 1988Watt & Green, 1982;Yuspa et al, 1989) and ectocervix (Choo et al, 1993;Kasturi et al, 1993). Moreover, it appears to have importance in vivo, as calcium gradients have been described in stratifying squamous epithelial tissues (Malmqvist et al, 1984; M e n o n et al., 1985). In vitro, calcium promotes increased differentiation of normal and HPV-16-immortalized ectocervical cells as measured by increased cornified envelope formation and increased K13, INV and TG1 levels Choo et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…When 90% confluent they were shifted to experimental medium containing low (panel L; 0.06 mM) or high (panel H; l'4mM) calcium and grown until 10 days postconfluence. Phase contrast images were then photographed at a magnification of x 100. calcium concentration is significantly higher in the superficial layer than in the basal layer Malmqvist et al, 1984;Menon et al, 1985); the higher concentration appears to be important in inducing cell differentiation, and as the cells differentiate they become increasingly permeable to Ca ~+. Patch-clamp experiments (Mauro et al, 1993) indicate the presence of a Ca2+-activated cation channel and a C1-channel in keratinocytes.…”

Section: Introductionmentioning

confidence: 99%

Differentiation-independent Constitutive Expression of the Human Papillomavirus Type 16 E6 and E7 Oncogenes in the CaSki Cervical Tumour Cell Line

Choo¹,

Rorke²,

Eckert

1994

Journal of General Virology

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CaSki cells are a human papillomavirus type 16 (HPV-16)-positive cell line that serves as a model for the study of advanced cervical carcinoma. Calcium is an important regulator of normal ectoeervical epithelial cell differentiation. HPV E6 and E7 gene products are thought to be important in the process of cervical cell immortalization and hence important in the development of cervical cancer. In the present study we examine the relationship between CaSki cell differentiation and expression of the papillomavirus oncogenes. Shifting CaSki cells from medium containing low (0.06 mM) to high (1"4 mM) calcium results in an increase in cell-cell contact and increased differentiation as measured by an increase in the level of mRNA encoding cytokeratin K13, involucrin and type 1 transglutaminase, which are markers of differentiation in the cervical epithelium. In contrast, E6/E7 transcripts are produced in a differentiation-independent constitutive manner. These results and those from our previous experiments with HPV-16-immortalized but non-tumorigenic cell lines suggest that the constitutive, differentiation-independent expression of E6/E7 levels is a property of both tumorigenic and non-tumorigenic HPV-16-positive cancer cells.

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“…During epidermal differentiation, keratinocytes move from a low calcium environment to layers containing progressively higher concentrations of calcium (Malmqvist et al, 1984;Menon et al, 1985). This spatial change in ion levels is associated with irreversible changes in cell phenotype characterized by alterations in cytokeratin expression, growth arrest, and cornification (Fuchs, 1990).…”

Section: Introductionmentioning

confidence: 99%

Modulation of intracellular calcium levels inhibits secretion of collagenase 1 by migrating keratinocytes.

Sudbeck

Pilcher

Pentland

et al. 1997

MBoC

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Calcium concentration influences keratinocyte differentiation, and, following injury, keratinocytes move through an environment of changing calcium levels. Because these migrating cells in wounds invariably express collagenase 1, we assessed if modulation of calcium levels regulates collagenase 1 production by primary human keratinocytes. Accurately reflecting the confined spatial pattern of enzyme production seen in vivo, collagenase 1 mRNA was expressed only by keratinocytes migrating from foci of differentiated cells. Treatment with calcium ionophores A23187 or thapsigargin markedly inhibited the basal and phorbol 12-myristate 13-acetate-(PMA) stimulated accumulation of keratinocyte collagenase 1 in the medium but did not affect collagenase 1 production by control or PMA-treated fibroblasts. A23187-mediated inhibition of collagenase 1 protein was not associated with a decrease in mRNA levels but rather was controlled by a selective and reversible block of enzyme secretion. This block in secretion was likely not due to altered protein folding as the proenzyme within A23187-treated cells remained capable of autolytic activation upon treatment with p-aminophenylmercuric acetate. In contrast, 92-kDa gelatinase mRNA and secreted protein levels were coordinately reduced by A23187. Keratin 14 expression, a basal keratinocyte marker, was reduced with PMA treatment, but A23187 did not affect keratin 14 expression. In human wounds, both basal and suprabasal keratinocytes at the migrating front of epidermis stained for keratin 14, but only the basal cells expressed collagenase 1. These data suggest that collagenase 1 production is not necessarily linked with expression of basal cell markers and that modulation of intracellular calcium levels can block secretion of collagenase 1 by keratinocytes which have moved away from the stratum basalis and from their natural substrate.

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Proton and electron microprobe analysis of human skin

Cited by 62 publications

References 8 publications

PKCδ Activation

PKCδ Activation

Differentiation-independent Constitutive Expression of the Human Papillomavirus Type 16 E6 and E7 Oncogenes in the CaSki Cervical Tumour Cell Line

Modulation of intracellular calcium levels inhibits secretion of collagenase 1 by migrating keratinocytes.

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