Isoforms of cathepsin D and human epidermal differentiation

Horikoshi, Tsutomu; Arany, István; Rajaraman, S.; Chen, San-Hwan; Brysk, Henry; Liu, Gang; Tyring, Stephen K.; Brysk, Miriam M.

doi:10.1016/s0300-9084(98)80013-8

Cited by 59 publications

(52 citation statements)

References 31 publications

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“…transforming growth factor-α (TGF-α), tumor necrosis factor-α (TNF-α), epidermal growth factor (EGF), fibroblast growth factors (FGFs), interleukin-1 α and β (IL-1 α and β), interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein (MCP-1), and macrophage inflammatory protein (MIP-1 α) expression increase during wound healing and thus play a role in localized as well as systemic inflammatory and immunologic effects (Ansel et al, 1990;Gharaee-Kermani and Phan, 2001). The presence of different CD isoforms has been reported at various stages of epidermal differentiation (Horikoshi et al, 1998). The importance of pCD or CD was established in CD-deficient mice that showed an impaired stratum corneum (Egberts et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…The presence of the 52-kDa form was shown in the spinous layer and activation occurred in the granular layer (48 kDa and 33 kDa form). These two active forms were present in the stratum corneum, where they played a role in epidermal desquamation (Horikoshi et al, 1998;Igarashi et al, 2004). Although, the role of CD in epidermal differentiation has been defined, the presence of pCD at different stages of differentiation is still unclear.…”

Section: Introductionmentioning

confidence: 99%

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Procathepsin D secreted by HaCaT keratinocyte cells – A novel regulator of keratinocyte growth

Vashishta¹,

Ohri²,

Větvičková³

et al. 2007

European Journal of Cell Biology

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Procathepsin D (pCD), the precursor form of lysosomal aspartic protease, is overexpressed and secreted by various carcinomas. The fact that secreted pCD plays an essential role in progression of cancer has been established. In this study, we describe substantial secretion of pCD by the human keratinocyte cell line HaCaT, under serum-free conditions. Moreover, exogenous addition of purified pCD enhanced the proliferation of HaCaT cells. The proliferative effect of pCD was inhibited by a monoclonal antibody against the activation peptide (AP) of pCD. Treatment of HaCaT cells with pCD or AP led to the secretion of a set of cytokines that might promote the growth of cells in a paracrine manner. The role of secreted pCD and its mechanism of action were studied in a scratch wound model and the presence of pCD and AP enhanced regeneration, while this effect was reversed by the addition of anti-AP antibody. Expression and secretion of pCD was upregulated in HaCaT cells exposed to various stress conditions. Taken together, our results strongly suggest that the secretion of pCD is not only linked to cancer cells but also plays a role in normal physiological conditions like wound healing and tissue remodeling.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Procathepsin D secreted by HaCaT keratinocyte cells – A novel regulator of keratinocyte growth

Vashishta¹,

Ohri²,

Větvičková³

et al. 2007

European Journal of Cell Biology

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“…The deposits of cathepsin B in epithelial cells and of cathepsin D in myofibroblasts might reflect participation of these proteinases in cellular processes involved in tissue remodelling, i.e. intracellular processes during proliferation or differentiation of cells [38]. In a study on bleomycin-induced lung fibrosis in hamsters, it was shown that fibroblast proliferation ceased y3 weeks after treatment [39].…”

Section: Discussionmentioning

confidence: 99%

Cathepsins in bleomycin-induced lung injury in rat

Koslowski¹,

Knoch²,

Kuhlisch³

et al. 2003

Eur Respir J

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Cathepsins in bleomycin-induced lung injury in rat. R. Koslowski, K. Knoch, E. Kuhlisch, D. Seidel, M. Kasper. #ERS Journals Ltd 2003. ABSTRACT: Endogenous inhibitors tightly control the activity of proteinases in the extracellular space. Proteinase/antiproteinase imbalance may be caused by predominance of proteinases, resulting in severe tissue damage or abundance of proteinase inhibitors, leading to a shift in the balance of synthesis and degradation of extracellular matrix proteins and accumulation of these matrix components. Lung fibrosis is characterised by accumulation of fibrous matrix proteins in the alveolar interstitium.The activity of cathepsin D and amounts of cathepsins D and B in bleomycin-injured rat lung tissue and alveolar macrophages were examined. In addition, the activities of cathepsins and cysteine proteinase inhibitors (CPIs) in bronchoalveolar lavage fluid (BALF) were determined.No cathepsin but high CPI activity and large amounts of procathepsin B were detected in the BALF. In the alveolar lumen, the disturbed proteinase/antiproteinase balance for cysteine proteinases was clearly dominated by CPIs. In alveolar macrophages, the main source of increased cathepsin levels, large changes in cathepsin B and D content were observed during the inflammatory phase, corresponding to the occurrence of procathepsin B in BALF. With the end of the phase of tissue remodelling, imbalances in cathepsin and CPI activities were largely eliminated. Immunoblot data, revealing an increase in cathepsin D levels in myofibroblast-like cells compared to fibroblasts and in resting fibroblasts compared to proliferating cells, implicate this proteinase in the differentiation and conversion processes occurring at the beginning of the fibrotic phase of lung injury.The results show that cathepsin amounts and activities are increased transiently in lung tissue during regeneration processes in bleomycin-induced lung injury. Imbalances of cathepsin and cysteine proteinase inhibitors activities are also a phenomenon of the phase of tissue remodelling initiated by lung injury.

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“…It was suggested that CTSD may be involved in the control of cell differentiation during normal development. Horikoshi et al found increased expression and increased activity of CTSD isoforms in the skin depending on the stage of epidermal differentiation (Horikoshi et al, 1998). CTSD enzyme is active at an acid pH (maximum at pH 3) and may work at the transition of the stratum granulosum to stratum corneum, because the stratum corneum produces an acid environment (pH 5.5) (Öhmann and Valquist, 1994).…”

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confidence: 99%

Cathepsin D is involved in the regulation of transglutaminase 1 and epidermal differentiation

Egberts

Heinrich

Jensen

et al. 2004

Journal of Cell Science

116

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We previously demonstrated that the aspartate protease cathepsin D is activated by ceramide derived from acid sphingomyelinase. Increased expression of cathepsin D in the skin has been reported in wound healing, psoriasis and skin tumors. We explored specific functions of cathepsin D during epidermal differentiation. Protein expression and enzymatic activity of cathepsin D increased in differentiated keratinocytes in both stratified organotypic cultures and in mouse skin during epidermal barrier repair. Treatment of cultured keratinocytes with exogenous cathepsin D increased the activity of transglutaminase 1, known to cross-link the cornified envelope proteins involucrin and loricrin during epidermal differentiation. Inhibition of cathepsin D by pepstatin A suppressed the activity of transglutaminase 1. Cathepsin D-deficient mice revealed reduced transglutaminase 1 activity and reduced protein levels of the cornified envelope proteins involucrin and loricrin. Also, amount and distribution of cornified envelope proteins involucrin, loricrin, filaggrin, and of the keratins K1 and K5 were significantly altered in cathepsin D-deficient mice. Stratum corneum morphology in cathepsin D-deficient mice was impaired, with increased numbers of corneocyte layers and faint staining of the cornified envelope only, which is similar to the human skin disease lamellar ichthyosis. Our findings suggest a functional link between cathepsin D activation, transglutaminase 1 activity and protein expression of cornified envelope proteins during epidermal differentiation.

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Isoforms of cathepsin D and human epidermal differentiation

Cited by 59 publications

References 31 publications

Procathepsin D secreted by HaCaT keratinocyte cells – A novel regulator of keratinocyte growth

Procathepsin D secreted by HaCaT keratinocyte cells – A novel regulator of keratinocyte growth

Cathepsins in bleomycin-induced lung injury in rat

Cathepsin D is involved in the regulation of transglutaminase 1 and epidermal differentiation

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