The Hsp90 inhibitor 17‐AAG represses calcium‐induced cytokeratin 1 and 10 expression in HaCaT keratinocytes

Miyoshi, Sadanori; Yamazaki, Shota; Uchiumi, A.; Katagata, Yohtaro

doi:10.1016/j.fob.2012.03.002

Cited by 8 publications

(4 citation statements)

References 27 publications

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“…HSPC inhibition by 17-AAG (a geldanamycin derivative) in HaCaT cells blocked calcium-induced differentiation. This observation suggests that HSPC can contribute to early stages of keratinocyte differentiation (Miyoshi et al 2012). The expression of HSPC was also found sensitive to disruption of skin barrier caused by tape stripping of stratum corneum (Dickel et al 2010).…”

Section: Essentials About Hspc1 (Hsp90α) and Hspc3 (Hsp90β) Proteinsmentioning

confidence: 96%

Heat shock proteins in the physiology and pathophysiology of epidermal keratinocytes

Ścieglińska

Krawczyk

Sojka

et al. 2019

Cell Stress and Chaperones

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Heat shock proteins (HSPs), a large group of highly evolutionary conserved proteins, are considered to be main elements of the cellular proteoprotection system. HSPs are encoded by genes activated during the exposure of cells to proteotoxic factors, as well as by genes that are expressed constitutively under physiological conditions. HSPs, having properties of molecular chaperones, are involved in controlling/modulation of multiple cellular and physiological processes. In the presented review, we summarize the current knowledge on HSPs in the biology of epidermis, the outer skin layer composed of stratified squamous epithelium. This tissue has a vital barrier function preventing from dehydratation due to passive diffusion of water out of the skin, and protecting from infection and other environmental insults. We focused on HSPB1 (HSP27), HSPA1 (HSP70), HSPA2, and HSPC (HSP90), because only these HSPs have been studied in the context of physiology and pathophysiology of the epidermis. The analysis of literature data shows that HSPB1 plays a role in the regulation of final steps of keratinization; HSPA1 is involved in the cytoprotection, HSPA2 contributes to the early steps of keratinocyte differentiation, while HSPC is essential in the reepithelialization process. Since HSPs have diverse functions in various types of somatic tissues, in spite of multiple investigations, open questions still remain about detailed roles of a particular HSP isoform in the biology of epidermal keratinocytes.

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Section: Essentials About Hspc1 (Hsp90α) and Hspc3 (Hsp90β) Proteinsmentioning

confidence: 96%

Heat shock proteins in the physiology and pathophysiology of epidermal keratinocytes

Ścieglińska

Krawczyk

Sojka

et al. 2019

Cell Stress and Chaperones

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“…The detection of FLG might be linked with reaching cell confluence since, during cultivation, the differentiation process may be induced. So FLG may be detected in low concentrations in undifferentiated cells, including the HaCaT line 36 , 37 . In agreement, we detected FLG with low NSAF value only in one out of the three technical repeats.…”

Section: Resultsmentioning

confidence: 99%

Comparative proteoinformatics revealed the essentials of SDS impact on HaCaT keratinocytes

Shkrigunov

Kisrieva

Samenkova

et al. 2022

Sci Rep

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There is no direct evidence supporting that SDS is a carcinogen, so to investigate this fact, we used HaCaT keratinocytes as a model of human epidermal cells. To reveal the candidate proteins and/or pathways characterizing the SDS impact on HaCaT, we proposed comparative proteoinformatics pipeline. For protein extraction, the performance of two sample preparation protocols was assessed: 0.2% SDS-based solubilization combined with the 1DE-gel concentration (Protocol 1) and osmotic shock (Protocol 2). As a result, in SDS-exposed HaCaT cells, Protocol 1 revealed 54 differentially expressed proteins (DEPs) involved in the disease of cellular proliferation (DOID:14566), whereas Protocol 2 found 45 DEPs of the same disease ID. The ‘skin cancer’ term was a single significant COSMIC term for Protocol 1 DEPs, including those involved in double-strand break repair pathway (BIR, GO:0000727). Considerable upregulation of BIR-associated proteins MCM3, MCM6, and MCM7 was detected. The eightfold increase in MCM6 level was verified by reverse transcription qPCR. Thus, Protocol 1 demonstrated high effectiveness in terms of the total number and sensitivity of MS identifications in HaCaT cell line proteomic analysis. The utility of Protocol 1 was confirmed by the revealed upregulation of cancer-associated MCM6 in HaCaT keratinocytes induced by non-toxic concentration of SDS. Data are available via ProteomeXchange with identifier PXD035202.

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“…From this protein network, two proteins were assessed as very closely related to cellular differentiation, namely heat shock protein 90 alpha (hsp90), for which an influence on CK formation has already been postulated [25], and FKBP1A, which directly interacts with the TGFβ receptor (▶ Fig. 6).…”

Section: Resultsmentioning

confidence: 99%

Cryptotanshinone from Salvia miltiorrhiza Roots Reduces Cytokeratin CK1/10 Expression in Keratinocytes by Activation of Peptidyl-prolyl-cis-trans-isomerase FKBP1A

et al. 2018

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Cryptotanshinone (CTS) (1 µM) from the roots of exerts a strong influence on the terminal differentiation of human keratinocytes (HaCaT cell line, primary natural human keratinocytes) and downregulates the expression of differentiation-specific cytokeratins CK1 and CK10 on protein and gene level. Other differentiation specific proteins as involucrin, filaggrin, loricrin, and transglutaminase were not affected to a higher extent. CTS (1 µM) did not influence the cell viability and the proliferation of keratinocytes. Using a combination of drug affinity response target stability assay in combination with a proteomic approach and multivariate statistics for target elucidation, peptidyl-prolyl-cis-trans-isomerase FKBP1A (known target of inhibitors such as tacrolimus or rapamycin) was addressed as potential molecular target of CTS. The interaction of CTS with FKBP1A was additionally shown by thermal shift and enzymatic activity assays. Interestingly, CTS served as an activator of FKBP1A, which led to a reduced activity of the TGF receptor pathway and therefore to a diminished CK1 and CK10 expression. The combination of the FKBP1A activator CTS with the inhibitor tacrolimus neutralized the effects of both compounds. From these data, a potential dermatological use of CTS and CTS-containing plant extracts (e.g., hydroalcoholic extract from the roots ) for keratinopathic ichthyosis, a disease characterized by overexpression of CK1 and CK10, is discussed. This study displays an experimental strategy for combining phytochemical aspects on active natural products with systematic identification of molecular targets on gene, protein, and cell level.

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The Hsp90 inhibitor 17‐AAG represses calcium‐induced cytokeratin 1 and 10 expression in HaCaT keratinocytes

Cited by 8 publications

References 27 publications

Heat shock proteins in the physiology and pathophysiology of epidermal keratinocytes

Heat shock proteins in the physiology and pathophysiology of epidermal keratinocytes

Comparative proteoinformatics revealed the essentials of SDS impact on HaCaT keratinocytes

Cryptotanshinone from Salvia miltiorrhiza Roots Reduces Cytokeratin CK1/10 Expression in Keratinocytes by Activation of Peptidyl-prolyl-cis-trans-isomerase FKBP1A

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