Downregulation of SMAD2, 4 and 6 mRNA and TGFβ Receptor I mRNA in Lesional and Non-lesional Psoriatic Skin

Yu, Haiyan; Mrowietz, Ulrich; Seifert, Oliver

doi:10.2340/00015555-0634

Cited by 19 publications

(16 citation statements)

References 25 publications

(26 reference statements)

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“…We also M Jiang et al observed lower phosphorylation of SMAD2/3 in psoriatic epidermis compared with healthy controls. Yu et al (2009) showed that the mRNA levels of SMAD2, 4, and 6 were downregulated in lesional and nonlesional psoriatic skin, whereas our data found no significant change in the mRNA levels of SMAD2, 4, 6, and 7 in psoriatic epidermis compared with healthy controls. This discrepancy may be due to samples from psoriatic patients being from different stages and severities.…”

Section: Discussioncontrasting

confidence: 82%

TGFβ/SMAD/microRNA-486-3p Signaling Axis Mediates Keratin 17 Expression and Keratinocyte Hyperproliferation in Psoriasis

Jiang

Sun

Dang

et al. 2017

Journal of Investigative Dermatology

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Keratin 17 (K17) is strongly expressed in psoriatic lesions but not healthy skin, and plays a crucial role in disease pathogenesis. The mechanism of aberrant K17 expression in psoriasis has not been fully elucidated. MicroRNAs are short, single-stranded, noncoding RNAs that play important roles in regulating gene expression. Psoriasis exhibits a specific microRNA expression profile distinct from that of healthy skin. In this study, we showed that miR-486-3p was markedly reduced in psoriatic epidermis and negatively correlated with the psoriasis area and severity index score. Its expression repressed K17 protein expression and decreased proliferation in a keratinocyte cell line overexpressing K17 (LV K17) compared with controls. Our data indicated that miR-486-3p was regulated by a transforming growth factor-β (TGFβ)/SMAD pathway and possibly mediated the downregulation of K17 protein in TGFβ-treated keratinocytes. Finally, the decreased expression of TGFβ receptor I in psoriatic epidermis inactivated the TGFβ/SMAD pathway, leading to K17 overexpression and cell proliferation. Collectively, our findings demonstrated that a TGFβ/SMAD/miR-486-3p signaling axis in keratinocytes regulated K17 expression and cell proliferation. We conclude that the loss of miR-486-3p in psoriatic epidermis leads to K17 protein overexpression and contributes to the pathogenesis of psoriasis. Overexpression of miR-486-3p may therefore be a therapeutic option for psoriasis.

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Section: Discussioncontrasting

confidence: 82%

TGFβ/SMAD/microRNA-486-3p Signaling Axis Mediates Keratin 17 Expression and Keratinocyte Hyperproliferation in Psoriasis

Jiang

Sun

Dang

et al. 2017

Journal of Investigative Dermatology

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“…4). For example, Smad6 was associated with keratinocytes15; Myod1, with alveolar rhabdomyosarcoma16; and Hnf4a, with lipoproteins17.…”

Section: Resultsmentioning

confidence: 99%

Generation of mouse ES cell lines engineered for the forced induction of transcription factors

Correa-Cerro

Piao

Sharov

et al. 2011

Sci Rep

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Here we report the generation and characterization of 84 mouse ES cell lines with doxycycline-controllable transcription factors (TFs) which, together with the previous 53 lines, cover 7–10% of all TFs encoded in the mouse genome. Global gene expression profiles of all 137 lines after the induction of TFs for 48 hrs can associate each TF with the direction of ES cell differentiation, regulatory pathways, and mouse phenotypes. These cell lines and microarray data provide building blocks for a variety of future biomedical research applications as a community resource.

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“…Our results confirmed such Th1/Th17 cytokine profile in psoriatic sera, which is also consistent with the previous report . These cytokines regulate the expression of membrane receptors in keratinocytes , which may consequently alter the reaction of keratinocytes to stimuli signals. The enhancement effect of TWEAK on cell proliferation is seen at the combination with psoriatic cytokines (M5).…”

Section: Discussionmentioning

confidence: 99%

TWEAK/Fn14 activation induces keratinocyte proliferation under psoriatic inflammation

Cheng

Liu

et al. 2015

Experimental Dermatology

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Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) has been reported to induce keratinocyte apoptosis in vitro by engaging its sole receptor of fibroblast growth factor-inducible 14 (Fn14). In this study, we explored the role of TWEAK/Fn14 pathway in the growth of psoriatic keratinocytes that is, however, characterized by suppressed apoptotic cell death. Skin tissues from the patients with psoriasis or healthy donors were determined for TWEAK and Fn14 expression, and primary keratinocytes were evaluated under the stimulation of psoriatic proinflammatory cytokines or plus TWEAK. The results showed that both TWEAK and Fn14 were highly expressed in psoriatic skins. Moreover, the stimulation of psoriatic cytokines enhanced Fn14 expression by keratinocytes in vitro, which expressed TNF receptor 2 predominantly and proliferated increasingly with the addition of TWEAK. Furthermore, TWEAK stimulation enhanced the synthesis of survivin, inhibitor of apoptosis protein 2 and cellular FLICE-inhibitory protein in lesional keratinocytes. Therefore, TWEAK/Fn14 interaction prefers to enhance proliferation but not apoptosis of keratinocytes under psoriatic inflammation. The activation of nuclear factor-κB signalling-dependent anti-apoptotic proteins and biased expression of TNF receptors may be responsible for such a novel principle in keratinocytes under psoriatic inflammation.

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Downregulation of SMAD2, 4 and 6 mRNA and TGFβ Receptor I mRNA in Lesional and Non-lesional Psoriatic Skin

Cited by 19 publications

References 25 publications

TGFβ/SMAD/microRNA-486-3p Signaling Axis Mediates Keratin 17 Expression and Keratinocyte Hyperproliferation in Psoriasis

TGFβ/SMAD/microRNA-486-3p Signaling Axis Mediates Keratin 17 Expression and Keratinocyte Hyperproliferation in Psoriasis

Generation of mouse ES cell lines engineered for the forced induction of transcription factors

TWEAK/Fn14 activation induces keratinocyte proliferation under psoriatic inflammation

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