CircEIF5 contributes to hyperproliferation and inflammation of keratinocytes in psoriasis via p-NFκB and p-STAT3 signalling pathway.

Psoriasis is a chronic, immune-mediated skin disease accompanied by hyperproliferation and inflammation of keratinocytes. Circular RNAs (circRNAs) as new players regulating the development of psoriasis have been reported in recent years. However, its mechanism has not yet been fully revealed. In this study, we identified that hsa_circ_0033469 (circEIF5) was highly expressed in psoriasis tissues compared with the normal skin. We investigated the functional roles of circEIF5 in proliferation and inflammatory of HaCat cells under M5-stimulated inflammatory condition. By using a approach of knockdown and overexpression of circEIF5, we showed that circEIF5 could promote proliferation by facilitating the G1/S transition and increase secretion of chemokines in HaCat cells. These moderating effects of circEIF5 were associated with the activating of the NF-κB and STAT3 signalling pathways. Moreover, NF-κB and STAT3 inhibition abrogated circEIF5-induced promotion of cell proliferation and chemokine secretion. These results indicated that through NF-κB and STAT3 signalling pathways, circEIF5 regulated the proliferation and chemokine secretion of HaCat cells and contributed to the pathogenesis of psoriasis, which might become a potent target for psoriasis treatment.

The lncRNA H19/miR-766-3p/S1PR3 Axis Contributes to the Hyperproliferation of Keratinocytes and Skin Inflammation in Psoriasis via the AKT/mTOR Pathway.

BACKGROUND: The pathogenesis of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are well studied in psoriasis. However, little is known about how specific lncRNAs and miRNAs affect the mechanism of psoriasis development and which pathways are involved. OBJECTIVES: To explore the role of the lncRNA H19/miR-766-3p/S1PR3 axis in psoriasis. METHODS: miRNA and lncRNA microarrays were performed using IL-22-induced HaCaT cells and psoriatic lesions, respectively. Fluorescence in situ hybridization and quantitative reverse-transcriptase polymerase chain reaction were used to detect the expression of miR-766-3p and lncRNA H19. Luciferase reporter assays were used to identify miR-766-3p/lncRNA H19 and miR-766-3p/S1PR3 combinations. CCK-8 and ELISA were performed to evaluate the proliferation of keratinocytes and the secretion of pro-inflammatory cytokines. Western blot analysis was used to detect the expression of S1PR3 and its downstream effector proteins. RESULTS: MiR-766-3p was upregulated in both HaCaT cells treated with the psoriasis-related cytokine pool (IL-17A, IL-22, IL-1 alpha, oncostatin M, and TNF-alpha) and tissues. Overexpression of miR-766-3p promoted keratinocyte proliferation and IL-17A and IL-22 secretion. LncRNA H19 and S1PR3 were demonstrably combined with miR-766-3p by luciferase reporter assay. lncRNA H19 repressed proliferation and inflammation, which were reduced by the miR-766-3p. AKT/mTOR pathway effected proliferation and inflammation by the lncRNA H19/miR-766-3p/S1PR3 axis. CONCLUSIONS: We established that downregulation of lncRNA H19 promoted the proliferation of keratinocytes and skin inflammation by up-regulating miR-766-3p expression levels and inhibiting activation of S1PR3 through the AKT/mTOR pathway in psoriasis.

Long Non-Coding RNA-GDA-1 Promotes Keratinocyte Proliferation and Psoriasis Inflammation by Regulating the STAT3/NF-κB Signaling Pathway via Forkhead Box M1.

Psoriasis is a chronic inflammatory skin disease associated with multiple comorbidities and complex pathogenesis. Long non-coding RNAs (lncRNAs) play an important regulatory role in many diseases, including psoriasis. In this study, We aimed to investigate the role and mechanism of lncRNA GDA-1 (GDA) in M5-treated psoriatic keratinocytes. GDA expression was significantly upregulated in psoriatic tissues and M5-treated keratinocytes. By silencing and overexpressing GDA in NHEKs and Ker-CT cells, we showed that GDA regulated proliferation and cell cycle and increased secretion of interleukin-1ß (IL-1ß), IL-6, and chemokine ligands 2 and 20 (CCL2 and CCL20). RNA sequencing after GDA silencing led to the identification of a close regulatory relationship between GDA and Forkhead Box M1 (FOXM1). GDA significantly influenced FOXM1 expression at both mRNA and protein levels and activated STAT3/NF-κB signaling pathways. STAT3 and NF-κB inhibition abrogated GDA effects on keratinocyte proliferation and inflammation. In conclusion, our study is the first to report that Lnc-GDA-1 distinctly regulates FOXM1 expression and mediates proliferation and inflammation of psoriatic keratinocytes through the STAT3/NF-κB signaling pathway, which may be a potent target for psoriasis treatment.

KMT2C Induced by FABP5P3 Aggravates Keratinocyte Hyperproliferation and Psoriasiform Skin Inflammation by Upregulating the Transcription of PIK3R3.

The extensive involvement of lysine methyltransferase 2C (KMT2C) in the inflammatory response is well-documented. However, little is known about the role of KMT2C in psoriasis. We identified that KMT2C was significantly upregulated in the epidermis of psoriatic skin lesions and the psoriasiform cell model. KMT2C knockdown diminished keratinocyte proliferation and the secretion of IL-6, IL-8, CCL20, and S100A9 in vitro and in vivo. In psoriasiform keratinocytes, KMT2C promoted the transcription of PIK3R3 by regulating the enrichment of histone H3 lysine 4 trimethylation at the PIK3R3 promoter and histone 3 lysine 4 monomethylation at the enhancer. The PIK3R3/protein kinase B/NF-κB pathway is a vital step in KMT2C-mediated alleviation of cytokine-primed inflammation. The long noncoding RNA FABP5P3 sustained KMT2C mRNA stability by recruiting human antigen R. Furthermore, inhibition of KMT2C attenuated epidermal hyperplasia and skin inflammation in mice with psoriasis. Taken together, our findings indicated a link between KMT2C and psoriasis and opened the possibility of using KMT2C as a potential therapeutic target for psoriasis treatment.

Role of the long non-coding RNA, SPRR2C, based on an in vitro psoriatic keratinocyte cell model

Background: Psoriasis is a chronic inflammatory disease of the skin with complex pathogenesis. Long non-coding RNAs (lncRNAs) play an important regulatory role in the occurrence and progression of many diseases, as well as psoriasis. Objectives: This study aimed to investigate the role and mechanism of the lncRNA, SPRR2C, in M5-induced psoriatic keratinocytes. Materials & Methods: SPRR2C expression and subcellular localization was detected using FISH and qRT-PCR. Ker-CT and HaCaT cells stimulated by M5 (IL-17A, tumour necrosis factor-α, IL-1α, IL-22, and oncostatin-M) were used to establish a psoriatic cell model. CCK-8 assay, CFSE proliferation assay, flow cytometry, western blotting and ELISA were used to examine the effects of SPRR2C in the keratinocyte model. Results: SPRR2C was highly expressed in psoriatic samples and M5-induced psoriatic keratinocytes, and SPRR2C was mainly localised to the cytoplasm. In keratinocytes, SPRR2C regulated proliferation, cell cycle and apoptosis, and induced the expression of IL-1ß, IL-6, IL-8, CXCL2 and CCL20. Moreover, SPRR2C cellular effects were shown to be mediated by the PI3K/AKT/mTOR signalling pathway, based on experiments with the AKT-specific inhibitor, MK-2206, which was also shown to suppress overexpression of SPRR2C. Conclusion: Our results indicate that SPRR2C plays a regulatory role and is involved in the PI3K/AKT/mTOR signalling pathway in psoriatic keratinocytes, which may provide a potential diagnostic and therapeutic target for psoriasis.

CircOAS3 Regulates Keratinocyte Proliferation and Psoriatic Inflammation by Interacting with Hsc70 via the JNK/STAT3/NF-κB Signaling Pathway.

Psoriasis is a chronic inflammatory disease of the skin with a very complex pathogenesis. Circular RNAs (circRNAs) play important regulatory roles in many diseases, including psoriasis. In this study, we found that circOAS3 expression was significantly upregulated in both psoriatic tissues and M5-induced keratinocytes. Silencing circOAS3 in HaCaT and Ker-CT cells inhibited their viability, promoted apoptosis, and blocked the cell cycle from the G1 to the S phase. RNA pull-down and RNA immunoprecipitation (RIP) analyses led to the identification of a direct interaction between circOAS3 and heat shock cognate protein 70 (Hsc70). Silencing circOAS3 expression negatively influenced Hsc70 protein expression but not mRNA expression. circOAS3 knockdown suppressed the activation of the JNK/STAT3/NF-κB signaling pathway. circOAS3 or Hsc70 silencing led to downregulated protein IL-6 expression, thus reducing psoriatic inflammation in vitro. In conclusion, the interaction between circOAS3 and Hsc70 mediates the proliferation and psoriatic inflammation of HaCaT and Ker-CT cells through the JNK/STAT3/NF-κB signaling pathway, suggesting that circOAS3 or Hsc70 may be a promising therapeutic target for psoriasis.

ILF2 Contributes to Hyperproliferation of Keratinocytes and Skin Inflammation in a KLHDC7B-DT-Dependent Manner in Psoriasis.

Background: The extensive involvement of interleukin enhancer binding factor 2 (ILF2) in RNA stability and the inflammatory response is well documented. Aberrant long noncoding RNA (lncRNA) expression contributes to the pathogenesis of psoriasis. However, little is known about the role of ILF2 in psoriasis. Objective: To investigate the role of ILF2 and KLHDC7B-DT in psoriasis. Methods: LncRNA expression in psoriatic tissues was measured by lncRNA microarray and qRT-PCR. Normal human epidermal keratinocytes (NHEKs), HaCaT cells, and Ker-CT cells stimulated with M5 (IL-17A, IL-22, IL-1α, oncostatin M, and TNF-α) were used to establish a psoriasis model in vitro. Fluorescence in situ hybridization was used to detect the distribution of KLHDC7B-DT and ILF2 in keratinocytes. The proliferative effects of KLHDC7B-DT and ILF2 on keratinocytes were demonstrated by EdU assay and flow cytometry. ELISA was used to detect the secretion levels of cytokines. RNA pull-down and RNA immunoprecipitation (RIP) were used to detect the direct binding of KLHDC7B-DT with ILF2. Western blotting was used to detect the proteins related to STAT3/JNK signalling pathways. Results: ILF2 and KLHDC7B-DT were significantly overexpressed in psoriatic tissues and M5-induced keratinocytes. KLHDC7B-DT promoted the proliferation of keratinocytes and induced the secretion of IL-6 and IL-8. KLHDC7B-DT could directly bind to ILF2 and activate the STAT3 and JNK signalling pathways. KLHDC7B-DT expression was regulated by ILF2. M5-induced proliferation and inflammatory cytokine secretion in keratinocytes was inhibited after ILF2 knockdown. Furthermore, we found that ILF2 promoted keratinocyte proliferation and the inflammatory response in a KLHDC7B-DT-dependent manner. Conclusions: ILF2 and KLHDC7B-DT are involved in the hyperproliferation of keratinocytes and skin inflammation in psoriasis. In addition, ILF2 functions in a KLHDC7B-DT-dependent manner.

How demographic and clinical characteristics contribute to the recovery of post-stroke dysphagia?

ABSTRACT: According to the analysis to find out how demographic and clinical characteristics influent the dysphagia outcome after stroke, furthermore, giving some insights to clinical treatment.One hundred eighty post-stroke dysphagia (PSD) patients were enrolled in this retrospective study at the stroke rehabilitation department. The outcome measurements are beside water swallow test at discharge and length of stay at hospital. Twenty-five demographic and clinical variables were collected for this study. Logistic regression and multilinear regression were utilized to estimate models to identify the risk and protect predictors of PSD outcome.Mouth-opening degree, drooling severity scale (DSS) level, mini-mental state exam (MMSE) level, Barthel index and Berg balance scale were significant different between recovered and unrecovered group. Type of stroke, MMSE degree, DSS and hemoglobin level shown significant predictive value for PSD outcome in logistic regression. In addition, obstructive sleep apnea (OSA) and DSS degree were important risk factors for PSD outcome. Gender, body mass index, drinking, hypertension, recurrent stroke, water swallow test level on admission, Berg balance scale, DSS and days between onset to admission shown significant predictive value for length of stay of PSD patients.PSD outcome was influenced by type of stroke, MMSE degree, DSS and hemoglobin level significantly and obstructive sleep apnea act as an important risk role for PSD recovery.