Project description:To investigate the differential expression of circRNA in severe acne and its role in competitive endogenous RNA regulatory networks, we have employed RNA microarray technology as a discovery platform to identify genes
Project description:The mechanisms of inflammation in acne are not well understood. This study performed in two separate patient populations focused on the activation of adaptive and innate immunity in early inflamed acne. Biopsies were collected from lesional and non-lesional skin of acne patients. Psoriasis patients and healthy volunteers were included in the study for comparison (not included in the records). Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed with real-time qPCR (RT-PCR) in two separate patient populations. Cytokines involved in Th17 lineage differentiation (IL-1beta, IL-6, TGF-beta; IL23p19) were remarkably induced at the RNA level. In addition, pro-inflammatory cytokines (IL-8, TNF-α), Th1 markers (IL12p40, CXCR3, T-bet, IFN-gamma), T regulatory cell markers (Foxp3, IL-10, TGF-β) and antimicrobial peptides (S100A7, S100A9, LNC2, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway may play a pivotal role in the disease process, offering new targets of therapy.
Project description:The mechanisms of inflammation in acne are not well understood. This study performed in two separate patient populations focused on the activation of adaptive and innate immunity in early inflamed acne. Biopsies were collected from lesional and non-lesional skin of acne patients. Psoriasis patients and healthy volunteers were included in the study for comparison (not included in the records). Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed with real-time qPCR (RT-PCR) in two separate patient populations. Cytokines involved in Th17 lineage differentiation (IL-1beta, IL-6, TGF-beta; IL23p19) were remarkably induced at the RNA level. In addition, pro-inflammatory cytokines (IL-8, TNF-α), Th1 markers (IL12p40, CXCR3, T-bet, IFN-gamma), T regulatory cell markers (Foxp3, IL-10, TGF-β) and antimicrobial peptides (S100A7, S100A9, LNC2, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway may play a pivotal role in the disease process, offering new targets of therapy. Total of 24 chips. 12 patients : 2 biospies per patient: 1 lesional and 1 non lesional.
Project description:The pathogenesis of acne has been linked to multiple factors such as increased sebum production, inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. In an attempt to understand the specific genes involved in inflammatory acne, we performed gene expression profiling in acne patients. Skin biopsies were obtained from an inflammatory papule and from normal skin in six patients with acne. Biopsies were also taken from normal skin of six subjects without acne. Gene array expression profiling was conducted using Affymetrix HG-U133A 2.0 arrays comparing lesional to nonlesional skin in acne patients and comparing nonlesional skin from acne patients to skin from normal subjects. Within the acne patients, 211 genes are upregulated in lesional skin compared to nonlesional skin. A significant proportion of these genes are involved in pathways that regulate inflammation and extracellular matrix remodeling, and they include matrix metalloproteinases 1 and 3, IL-8, human beta-defensin 4, and granzyme B. These data indicate a prominent role of matrix metalloproteinases, inflammatory cytokines, and antimicrobial peptides in acne lesions. These studies are the first describing the comprehensive changes in gene expression in inflammatory acne lesions and are valuable in identifying potential therapeutic targets in inflammatory acne. Experiment Overall Design: total 18 chips. 6 for acne lesion samples, 6 for normal skin samples, 6 for non-acne patient normal skin samples
Project description:The pathogenesis of acne has been linked to multiple factors such as increased sebum production, inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. In an attempt to understand the specific genes involved in inflammatory acne, we performed gene expression profiling in acne patients. Skin biopsies were obtained from an inflammatory papule and from normal skin in six patients with acne. Biopsies were also taken from normal skin of six subjects without acne. Gene array expression profiling was conducted using Affymetrix HG-U133A 2.0 arrays comparing lesional to nonlesional skin in acne patients and comparing nonlesional skin from acne patients to skin from normal subjects. Within the acne patients, 211 genes are upregulated in lesional skin compared to nonlesional skin. A significant proportion of these genes are involved in pathways that regulate inflammation and extracellular matrix remodeling, and they include matrix metalloproteinases 1 and 3, IL-8, human beta-defensin 4, and granzyme B. These data indicate a prominent role of matrix metalloproteinases, inflammatory cytokines, and antimicrobial peptides in acne lesions. These studies are the first describing the comprehensive changes in gene expression in inflammatory acne lesions and are valuable in identifying potential therapeutic targets in inflammatory acne. Keywords: acne lesion, normal skin
Project description:Transplant rejection is a major factor limiting allograft survival. CircRNAs are reported to be strongly associated with various diseases pathogenesis. However, the potential role of circRNAs in cardiac transplant rejection are rarely reported. Here, differentially expressed mRNAs and circRNAs were determined by microarrays in allogeneic cardiac allografts. Functional analysis was then performed and a full-scale functional blueprint of the circRNA-associated-ceRNA networks was constructed. Among the circRNA networks, circ23123 expression was negatively linked with cytolytic molecules of CD8+ T cells by targeting miR155-SOCS1 axis. We illustrated a new comprehensive view of circRNAs and their potential functional impact in cardiac transplantation. It may provide a prospective for therapeutic strategy on organ transplant rejection in the future.
Project description:Purpose: Immunoglobulin A nephropathy (IgAN) is immune-mediated primary glomerulonephritis, which is the most common reason leading to renal failure worldwide, the exact pathogenesis of IgAN is not well defined. Accumulating evidence indicates that circular RNAs (circRNAs) play crucial roles in the immune disease by involving in the competing endogenous RNA (ceRNA) network mechanism. At present, the studies of the circRNA profiles and circRNA-associated ceRNA networks in the IgAN are still scarce. This study aimed to elucidate the potential roles of circRNA, microRNA (miRNA), and messenger RNA (mRNA) ceRNA network in peripheral blood mononuclear cells (PBMCs) of IgAN. Methods: CircRNA sequencing was used to identify the differential expressed circRNAs (DEcircRNAs) of PBMCs in IgAN and healthy controls. A circRNA-miRNA-mRNA ceRNA network was constructed to further investigate the mechanisms of IgAN. Results: A total of 145 circRNAs were differentially expressed in IgAN compared with controls (|log2 (FC)|>1 and P-value <0.05). Combined with the data from GSE73953 and GSE25590 in GEO database, a ceRNA network was constructed which contained 16 DEcircRNAs, 72 differential expressed mRNAs (DEmRNAs) and 11 differential expressed miRNAs (DEmiRNAs). Conclusion: Our study identified a novel circRNA-mediated ceRNA regulatory network mechanisms in the pathogenesis of IgAN.
Project description:Innate immune defense against deep tissue infection by Staphylococcus aureus is orchestrated by fibroblasts that become antimicrobial when triggered to differentiate into adipocytes. However, the role of this process in non-infectious human diseases is unknown. To investigate the potential role of adipogenesis by dermal fibroblasts in acne, a disorder triggered by Cutibacterium acnes (C. acnes), single-cell RNA-sequencing was performed on human acne lesions and mouse skin challenged by C. acnes. A transcriptome consistent with adipogenesis was observed within specific fibroblast subsets from human acne and mouse skin lesions infected with C. acnes. Perifollicular dermal preadipocytes in human acne and mouse skin lesions showed colocalization of PREF1, an early marker of adipogenesis, and cathelicidin (Camp), an antimicrobial peptide. This capacity of C. acnes to trigger production of cathelicidin in preadipocytes was dependent on TLR2. Treatment of wild-type mice with retinoic acid (RA) suppressed the capacity of C. acnes to form acne-like lesions, inhibited adipogenesis and enhanced cathelicidin expression in preadipocytes, but lesions were unresponsive in Camp-/- mice, despite the anti-adipogenic action of RA. Analysis of inflamed skin of acne patients after retinoid treatment also showed enhanced induction of cathelicidin, a previously unknown beneficial effect of retinoids in difficult-to-treat acne. Overall, these data provide evidence that adipogenic fibroblasts are a critical component of the pathogenesis of acne and represent a potential target for future therapy.
Project description:Objective Circular RNAs (circRNAs) are covalently closed, endogenous non-coding RNAs. CircRNAs play a vital role in liver diseases, acting as microRNA (miRNA) sponges. However, the angiogenic role of circRNA remains unknown in liver fibrosis and is the focus of this study. Methods Liver fibrosis was induced by thioacetamide (TAA), or carbon tetrachloride (CCl4) in mice. CircRNA-microarray, AGO2-RNA immunoprecipitation (RIP), and RNA-seq were utilized to explore the hepatic circRNAs profile. The qPCR and PCR-gel electrophoresis analysis were used to investigate the characterization of circRNA-007371. Liver tissues and EMOA murine endothelial cells were used to verify the angiogenic mechanism of circRNA-007371. Results The increased collagen deposition, pseudolobule formation, and angiogenesis were observed in murine liver induced by TAA and CCl4. CircRNA-microarray in TAA-induced fibrotic murine liver indicated that the expression of circRNA-007371 was up-regulated. Moreover, AGO2-RIP and PCR analysis showed that circRNA-007371 had the characterization of circRNAs and played a role as competing endogenous RNAs (ceRNA) sponging miR-200a. In vitro, circRNA-007371 promoted the ability of migration, growth, and blood vessel formation in EMOA murine endothelial cells using wound healing and tube formation assay. The AGO2-RIP and RNA-sequencing analysis in overexpression circRNA-007371 EMOA murine endothelial cells demonstrated that circRNA-007371 upregulates the stromal antigen 1 (Stag1) via spouse of miR-200a and HIF-1 signaling pathway might participate in the angiogenesis. Conclusions This study discovers that circRNA-007371, a novel ceRNA, is up-regulated, and enhances the angiogenesis via angiocrine role to regulate the STAG1-miR-200a-5p signaling pathway in liver fibrosis.