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aiming Zhang Shanxi Key Laboratory of Stem Cell for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, People's Republic of ChinaCorrespondence: Kaiming Zhang, Shanxi Key Laboratory of Stem Cell for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, No. 5 Dong San Dao Xiang, Jiefang Road, Taiyuan, Shanxi Province, People's Republic of China, Tel +86-351-5656080, Email [email protected] Background: Cell proliferation, migration, and angiogenesis are aberrant in psoriatic human dermal microvascular endothelial cells (HDMECs), resulting in abnormal endothelial function and microvascular dilation in psoriasis. Objective: To explore the role of Integrin subunit alpha 9 (ITGA9) in proliferation and migration of dermal microvascular endothelial cells. Methods: HDMECs were isolated from the skin of 6 psoriatic patients and 6 healthy controls. Expression levels of ITGA9 mRNA and protein were assessed with qRT-PCR and Western blot, respectively, while miqRT-PCR was used to determine expression levels of miR-146a-3p. Cell proliferation and migration were assessed in human microvascular endothelial cell line (HMEC-1), following overexpression of either ITGA9 or miR-146a-3p, or co-transfection with miR-146a-3p-mimic and pLVX - ITGA9. Cell viability was detected by Cell Counting Kit-8 assay and 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation assay. Cell apoptosis was assessed, using annexin V-FITC/PI apoptosis detection kit, while cell migration was detected by wound healing and transwell assay. Results: Expression levels of ITGA9 were significantly decreased in psoriatic HDMECs compared to normal controls. Moreover, expression levels of miR-146a-3p were higher in psoriatic HDMECs than in normal controls. Overexpression of miR-146a-3p lowered expression levels of ITGA9, accompanied by increased proliferation and migration of HMEC-1 in vitro. In contrast, overexpression of ITGA9 inhibited proliferation and migration of HMEC-1, while increasing expression levels of cdc42, ki67, focal adhesion kinase (FAK), c-Src tyrosine kinase (Src), RAC1 and RhoA. Conclusion: ITGA9 can repress the proliferation and migration of HMEC-1, suggesting utility of ITGA9 as a potential therapeutic intervention for psoriasis. [ABSTRACT FROM AUTHOR]

aiming Zhang21Shanxi Key Laboratory of Stem Cell for Immunological Dermatosis, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, 030009, People's Republic of China; 2Shanxi Key Laboratory of Stem Cell for Immunological Dermatosis, Taiyuan Central Hospital, Taiyuan, Shanxi Province, 030009, People's Republic of ChinaCorrespondence: Kaiming Zhang, Taiyuan Central Hospital, No, 5 Dong San Dao Xiang, Jiefang Road, Taiyuan, Shanxi Province, People's Republic of China, Tel +86-351-5656080, Email [email protected] Purpose: Psoriasis is a chronic recurring autoimmune skin disease with a complex etiology and chronic progression; however, its molecular mechanisms remain unclear. Patients and Methods: We performed transcriptomic analysis to profile the mRNA expression of psoriatic lesions (PL) and non-lesion (NL) tissues from psoriasis patients along with normal skin from healthy donors. RT-qPCR was used to validate the mRNA expression profiles. Results: A total of 237 differentially expressed genes were screened and identified by RNA sequencing. GO and KEGG analysis indicated that these DEGs were enriched in the PPAR signaling pathway and intermediate filament cytoskeleton. For PPAR signaling pathway, the expression of five genes, including ADIPOQ, AQP7, PLIN1, FABP4 and LPL, were all significantly decreased in psoriatic lesions compared to normal skin by RT-qPCR. There is a clear difference between psoriatic lesions and non-lesion in the expression of ADIPOQ, AQP7 and LPL. For intermediate filament cytoskeleton, including KRT27, KRT25, KRT71, KRT86 and KRT85 were significantly decreased in the psoriasis lesions, showing agreement with the RNA-seq data. Conclusion: This study revealed a significant difference between the mRNA expression profiles of PL, NL tissue and normal skin. [ABSTRACT FROM AUTHOR]

aiming Zhang21Shanxi Key Laboratory of Stem Cell for Immunological Dermatosis, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, 030009, Shanxi Province, People's Republic of China; 2Shanxi Key Laboratory of Stem Cell for Immunological Dermatosis, Taiyuan Central Hospital, Taiyuan, 030009, Shanxi Province, People's Republic of ChinaCorrespondence: Kaiming Zhang, Taiyuan Central Hospital, No, 5 Dong San Dao Xiang, Jiefang Road, Taiyuan, Shanxi Province, People's Republic of China, Tel +86-0351-5656080, Email [email protected] Purpose: Psoriasis is a multifactorial disease with a complex genetic predisposition. The pathophysiology of psoriasis is associated with genetic variants. To better characterize gene variants in psoriasis and identify the relationship between clinical characteristics and variant genes in its pathogenesis. Patients and Methods: DNA was extracted and purified from eight pairs of monozygotic twins with psoriasis discordance and 282 type I psoriasis patients. Thirteen variable genes were amplified and sequenced using the Sanger method after whole genome sequencing. Results: Thirteen genes were found to be variable in eight pairs of monozygotic twins with psoriasis discordance. Among the 13 genes, the variant frequencies of protein kinase C epsilon (PRKCE) (c.240T>C, 35.9% vs 47.7%, P < 0.05) and kinesin light chain 1 (KLC1) (c.216A>G, 2.9% vs 98.1%, P< 0.01) were significantly lower in psoriasis than in normal Asian individuals. Additionally, we found considerable differences in the relationship between variants in genes CADM2, JPH2, SPTLC3 and clinical characteristics stratified by medical history and family history. Moreover, the variants in MEGF6 (39.52% vs 22.50%, χ2=3.83, p < 0.05) showed a stronger association with the mild group (PASI ≤ 10) than the heavy group. Conclusion: Our results provide a comprehensive correlation analysis of regulatory genes that are regulated in psoriasis. This integrated analysis offers novel insight into the pathogenic mechanisms involved in psoriasis. Graphical [ABSTRACT FROM AUTHOR]

aiming Zhang, Guohua Yin Shanxi Key Laboratory of Stem Cell for Immunological Dermatosis, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, 030009, Shanxi Province, People's Republic of ChinaCorrespondence: Guohua Yin, Tel +86 0351-5656079, Email [email protected] Purpose: Previous studies showed the link of CD14+ monocytes to inflammation and oxidation in psoriasis. In the present study, we investigated the regulatory role of miR-155 in CD14+ monocyte function in psoriasis. Materials and Methods: CD14+ monocytes were isolated from peripheral blood by magnetic bead separation method and its function was assessed following silence of miR-155 by lentivirus transfection with or without inhibition of TLR4 pathway. CCK8 and EdU were used to assess the proliferation of CD14+ monocytes. Expression levels of SOCS1, TLR4 and MyD88 proteins were determined by Western blotting, while expression levels of IL-6, TNF-α, ROS, MDA and T-AOC were measured by ELISA kit. The expression levels of mRNA for miR-155, NF-κB and its subunit NF-κB-p65 were assessed by q-PCR. Results: The results showed that compared with normal control CD14+ monocytes, the expression levels of miR-155, NF-κB and NF-κB-p65, TLR4, MyD88 and IL-6, TNF-α were increased, while expression levels of SOCS1 were decreased in CD14+ monocytes from psoriatic patients. Enhanced cell proliferation and oxidation were also observed in CD14+ monocytes from psoriatic patients. Inhibition of miR-155 partially corrected the abnormalities of cell proliferation and expression levels of biomarkers mentioned above in CD14+ monocytes from psoriatic patients. Inhibitions of both TLR4 pathway and miR-155 further corrected abnormalities of proliferation and the above biomarkers in CD14+ monocytes from psoriatic patients. Conclusion: These results suggest that increased expression levels of miR-155 contribute to CD14+ monocyte-mediated inflammation and oxidation in psoriasis via TLR4 pathway. [ABSTRACT FROM AUTHOR]