Abstract:
BACKGROUND:Cutaneous T cell lymphoma (CTCL) comprises a heterogeneous group of skin-homing T cell tumors. The small guanosine triphosphate effector p21-activated kinase 1 (PAK1) plays an important role in many fundamental cellular functions, including cell motility, proliferation, and apoptosis. The expression of PAK1 is up-regulated in several types of human cancers. However, little is known about the role of PAK1 in the pathogenesis of CTCL. OBJECTIVE:The aim of this study was to evaluate the expression pattern and underlying mechanism of PAK1 in CTCL. METHODS:Quantitative real-time polymerase chain reaction(qRT-PCR) was used to detect PAK1 mRNA expression in the peripheral blood mononuclear cells (PBMCs) of patients with CTCL. The expression of PAK1 protein in CTCL tumor tissues was determined by immunohistochemistry. CTCL cell lines were treated with a small molecule inhibitor of PAK1, p21-activated kinase inhibitor III (IPA3), at concentrations of 2, 3.5 and 5 μM for 24 h. Hut 78 and HH CTCL cells were transfected with lentiviral-based PAK1 gene knockdown vectors. We determined the effects of PAK1 knockdown on cell proliferation and apoptosis in CTCL cells by MTS assay and flow cytometry. Animal experiments were performed to investigate the effects of PAK1 knockdown on the growth of tumors in vivo. Transcriptomic sequencing was performed to detect the direct downstream targets of PAK1 silencing. Reverse transcription polymerase chain reaction and western blot analysis were applied to verify the results of the transcriptomic analysis. RESULTS:We detected PAK1 overexpression in PBMCs and skin lesions from patients with CTCL compared with benign inflammatory dermatoses (BID). Knockdown of PAK1 inhibited cell proliferation and promoted spontaneous apoptosis. In addition, the inhibitory effect of IPA3 was validated in the CTCL cell lines. Additionally, mice injected with PAK1-silenced cells presented with a decreased rate of tumor growth compared with the control groups. Moreover, the mRNA and protein expression of PUMA (BBC3) and p21 (CDKN1A) were increased in PAK1-silenced Hut 78 and HH cells. CONCLUSIONS:Our data indicated that PAK1 is upregulated in CTCL. PAK1 silencing induced apoptosis and inhibited cell growth by stimulating the expression of PUMA and p21. Thus, PAK1 may be a potential tumor marker and therapeutic target of CTCL.
journal_name
J Dermatol Scijournal_title
Journal of dermatological scienceauthors
Wang Y,Gu X,Li W,Zhang Q,Zhang Cdoi
10.1016/j.jdermsci.2017.11.019subject
Has Abstractpub_date
2018-04-01 00:00:00pages
60-67issue
1eissn
0923-1811issn
1873-569Xpii
S0923-1811(18)30002-1journal_volume
90pub_type
杂志文章abstract:BACKGROUND:The capacity of photosensitizing chemicals with ultraviolet A light (UVA) to induce apoptosis is one of the methods to assess their phototoxic and potentially photoallergic properties, since apoptotic cells may be easily presented by antigen-presenting cells. OBJECTIVES:We examined the photoaggravated abili...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2006.10.010
更新日期:2007-02-01 00:00:00
abstract::Crude enzyme solutions of prolidase were extracted from cultured human skin fibroblasts derived from control and prolidase-deficient sisters. Two forms of prolidases (prolidase-I and II) were partially purified by high performance liquid chromatography equipped with an ion exchange column. On gel filtration, the relat...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(90)90588-5
更新日期:1990-09-01 00:00:00
abstract::It has been reported that cellular oxidative stress induces apoptosis. Ultraviolet radiation that generates reactive oxygen intermediates (ROIs) also induces apoptosis. Superoxide dismutase (SOD) is among the most active scavengers of ROIs, providing defense against the cellular oxidative stress. Mammalian cells expre...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(99)00060-2
更新日期:2000-05-01 00:00:00
abstract::Considerable evidence suggests that factor XIIIa, a blood coagulation factor, also functions in tissue repair, and specifically in the dynamic process of fibroplasia. On the other hand, the dynamic process of tissue expansion would require a loosening of the dermis, the opposite of fibroplasia. We examined the effects...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(91)90044-x
更新日期:1991-01-01 00:00:00
abstract::Telomeres, which exist in eukaryotic chromosome ends in specialized G-rich TTAGGG structure, protect the ends from degradation or fusion. On the other hand, telomerase is a ribonucleoprotein complex enzyme that synthesizes TTAGGG repeat sequences at the ends of eukaryotic chromosomes. Previous studies suggested that t...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(99)00049-3
更新日期:2000-02-01 00:00:00
abstract:BACKGROUND:Netherton syndrome (NS) is a rare but severe type of ichthyosis characterized by atopy, allergies, and potentially lethal skin overdesquamation associated with highly elevated proteolytic activities in LEKTI-deficient epidermis. NS symptoms are recapitulated in Spink5-/- mouse where the gene encoding Lekti h...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2019.06.004
更新日期:2019-07-01 00:00:00
abstract:BACKGROUND:The exact mechanism of the inflammatory changes occurring during the development of Behçet's disease (BD) remains unclear. OBJECTIVE:We investigated the role of classical (M1) and alternative (M2) activation of macrophages in a herpes simplex virus (HSV)-induced BD mouse model. METHODS:The classical vs. al...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2013.11.001
更新日期:2014-03-01 00:00:00
abstract::Etiology of connective tissue disease is unknown. The association of infectious agents has been suspected serologically, ultrastructurally and recently by means of molecular biological techniques. We extracted RNA from lesions of 25 discoid lupus erythematosus, 9 systemic LE, and 3 systemic sclerosis biopsies, and rev...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(95)00422-x
更新日期:1996-01-01 00:00:00
abstract::Using fetal rat keratinizing epidermal cells (FRSK cells) we investigated the effects of retinoids on the cyclic AMP system. The beta-adrenergic adenylate cyclase response was significantly decreased by the treatment of cells with 1 x 10(-6) M Ro 10-1670. The effect was observed by 12 h and remained for at least 48 h....
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(93)90080-9
更新日期:1993-04-01 00:00:00
abstract::We previously reported a simple and easy-to-use device, Scratch Monitor for evaluation of nocturnal scratching. In the present study, the effect of an antihistamine (azelastine hydrochloride) on atopic dermatitis was investigated using this device. In 40 patients with atopic dermatitis, nocturnal scratching was measur...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(99)00048-1
更新日期:1999-12-01 00:00:00
abstract::The vasculature in adult skin remains normally quiescent, due to the dominant influence of endogenous angiogenesis inhibitors over angiogenic stimuli. However, skin retains the capacity for brisk initiation of angiogenesis, the growth of new blood vessels from preexisting vessels, during tissue repair and in numerous ...
journal_title:Journal of dermatological science
pub_type: 杂志文章,评审
doi:10.1016/s0923-1811(00)00145-6
更新日期:2000-12-01 00:00:00
abstract:BACKGROUND:Several inhibitor of apoptosis proteins (IAPs) are cleaved during apoptosis. Studies of the melanoma-associated IAP (ML-IAP) Livin, using recombinant molecules, have implicated both caspases 3/7 and the serine protease Omi/HtrA2 in its proteolytic cleavage. OBJECTIVE:To characterize the apoptotic cleavage o...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2006.05.007
更新日期:2006-09-01 00:00:00
abstract::Quinolone antibacterial agents, known to elicit photosensitive dermatitis as an adverse effect, have both phototoxicity and photoallergenicity. The latter potency is mainly derived from their photohaptenic moiety; quinolones covalently bind to protein and cells upon exposure to ultraviolet A (UVA) light. Our previous ...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(99)00011-0
更新日期:1999-09-01 00:00:00
abstract::The ability of beta-carotene, lutein or astaxanthin to protect against UVA-induced oxidative stress in rat kidney fibroblasts (NRK) was assessed. Activities of the antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD), and changes in thiobarbituric acid reactive substances (TBARS) were measured as indices ...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(97)00058-3
更新日期:1998-03-01 00:00:00
abstract::Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental and skeletal anomalies, palmo-plantar pits, odontogenic keratocysts, ectopic calcification, and occurrence of various types of tumors including basal cell carcinoma. Recent evidence has indicated that the huma...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(01)00104-9
更新日期:2001-09-01 00:00:00
abstract:BACKGROUND:It is well known that cyclophosphamide (Cy) treatment before sensitization paradoxically enhances rather than suppresses contact hypersensitivity (CH) reactions. In fact, Cy-treated mice developed a significant (p < 0.05) increase of the CH reactions to 2,4,6-trinitro-1-chrolobenzene (TNCB) in comparison wit...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2005.02.002
更新日期:2005-08-01 00:00:00
abstract:BACKGROUND:Infection with different species of cutaneous human papillomaviruses (cHPV) of genus alpha (cαHPVs) and associated skin disease are highly prevalent in solid organ transplant recipients (OTR), documenting the importance of the immunological control of HPV infection. OBJECTIVES:To investigate the natural cou...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2014.11.002
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Hyperpigmentation is aesthetic undesirable. Sesamol and the standard antimelanogenic agent (kojic acid) were shown to hinder melanogenesis by blocking tyrosinase and reducing melanin content. OBJECTIVE:The FTIR microspectroscopy was used in an attempt to find a novel method to define biological alternation ...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2013.11.002
更新日期:2014-03-01 00:00:00
abstract:BACKGROUND:Pseudoxanthoma elasticum (PXE) is an inherited systemic disorder, characterized by dermal, ocular and cardiovascular lesions. Genetic defects of the ABCC6 (MRP6) transporter are known to cause PXE. OBJECTIVES:The purpose of this study was to identify the genetic background of a PXE patient with a very early...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2005.07.010
更新日期:2005-11-01 00:00:00
abstract:BACKGROUND:Psoriasis is a chronic inflammatory dermatosis that has been associated with various cardiovascular and metabolic comorbidities, including myocardial infarction, stroke, and diabetes mellitus. Recently, there are studies reporting the association of psoriasis with renal diseases. OBJECTIVE:To evaluate the r...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2015.03.012
更新日期:2015-06-01 00:00:00
abstract::Thiols are of great importance for the regulation of many cellular functions including metabolism, transport and cell protection. In this study the usefulness of L-cysteine methyl and octyl esters, of N,S-diacetyl-L-cysteine methyl ester and glutathione isopropyl ester as cellular cysteine and GSH delivery systems was...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(90)90008-2
更新日期:1990-01-01 00:00:00
abstract:BACKGROUND:Antimicrobial peptide derived from insulin-like growth factor binding protein-5 (AMP-IBP5) is a potent antimicrobial agent that possesses various immunomodulatory activities. The parent protein of AMP-IBP5, IGFBP-5, has been shown to exert its effects via an insulin-like growth factor-1 receptor-independent ...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2020.07.003
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:Foot ulcers are one of the main diabetes complications due to its high frequency and difficulty of complete healing. There are several factors that participate in diabetic ulcers development and limited information exists about the role of antimicrobial peptides (AMP) in its pathogenesis. OBJECTIVE:The aim ...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2011.09.013
更新日期:2012-01-01 00:00:00
abstract::Psoriatic involved epidermis has been characterized by a defective beta-adrenergic adenylate cyclase response. It is also characterized by increased cholera toxin- and forskolin-induced cyclic AMP accumulations. Due to the fact that receptor signals are transduced to adenylate cyclase through guanine nucleotides bindi...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(97)00069-8
更新日期:1998-05-01 00:00:00
abstract::The integrity of the epidermis depends on the cohesion between keratinocytes, and desmosomes are the main adhesion structures. When cells become cornified, desmosomes are modified and transformed into corneodesmosomes. Mutations in the genes encoding desmosomal components underlie several skin diseases including palmo...
journal_title:Journal of dermatological science
pub_type: 杂志文章,评审
doi:10.1016/j.jdermsci.2014.02.005
更新日期:2014-05-01 00:00:00
abstract:BACKGROUND:Optical coherence tomography (OCT) is a promising non-invasive imaging technique that has not systematically been studied in skin cancer such as basal cell carcinoma (BCC). OBJECTIVE:We aimed, first, to describe the in vivo histologic features of BCC by using OCT, and second, to find out whether it is possi...
journal_title:Journal of dermatological science
pub_type: 临床试验,杂志文章
doi:10.1016/j.jdermsci.2006.11.012
更新日期:2007-03-01 00:00:00
abstract:BACKGROUND:High doses of sun-emitted UV-radiation induce reactive oxygen species (ROS) as major pro-oxidants thus inducing premature skin aging. The best prevention of the destructive action of free radicals in human skin is textile coverings, topical sunscreens and the development of a high antioxidative protective ne...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2011.06.009
更新日期:2011-10-01 00:00:00
abstract::We have previously reported that two species of pro alpha 1(IV) collagen chains, disulfided (500 kDa) and non-disulfided (180 kDa), were produced by B16 melanoma cells (J Biochem (1994) 116; 1039-1043). The mechanism by which the non-disulfided pro alpha 1(IV) chain is produced was studied. No significant difference i...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(95)00486-6
更新日期:1996-10-01 00:00:00
abstract:BACKGROUND:Grafting of cultured epithelium has become a useful technique for the treatment of epithelial defects, since grafted epithelial cells secrete factors promoting wound healing. We identified one such factor produced by cultured oral epithelial cells as thrombospondin-1 (TSP-1). Recently, TSP-1 was reported to ...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(02)00150-0
更新日期:2003-04-01 00:00:00
abstract::Flank organs of male Golden Syrian hamsters contain sebaceous glands and hair follicles whose morphology and function are highly dependent on androgen, which makes these organs a useful model to study androgen action. In order to investigate molecular mechanisms of androgen action, we cloned a cDNA encoding the hamste...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(00)00172-9
更新日期:2001-07-01 00:00:00