Homo sapiens cultivar:SZ95
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ABSTRACT:
PROVIDER: PRJNA422197 | ENA |
REPOSITORIES: ENA
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Project description:The differential gene expression in SZ95 sebocytes under hypoxia include 256 genes, among them several lipid droplet-associated proteins. We detected 93 inflammatory mediators been regulated under hypoxia.
2020-08-19 | GSE113882 | GEO
Project description:Background: Acne Vulgaris is one of the commonest dermatological challenges lacking effective and well-tolerated treatment. An earlier study indicated that resveratrol (RVT) exhibits therapeutic effects in patients with acne through unknown mechanisms. Objectives: To evaluate the effects of RVT on linoleic acid (LA)-induced lipogenesis and peptidoglycan (PGN)-induced inflammation in cultured SZ95 sebocytes in vitro and to study the underlying mechanisms. Methods: Whole transcriptome analysis was performed with RNA-sequencing. Intracellular neutral lipids were detected by Nile red staining. Lipidomics was used to examine the changes of lipid profile in sebocytes. Interleukin (IL)-1β and IL-6 mRNA and protein levels were assessed by quantitative real-time PCR and Enzyme-Linked Immunosorbent Assay, respectively. Expressions of lipogenesis-related proteins inflammatory signaling pathway and AMP-activated protein kinase (AMPK) pathway were evaluated by Western blot. Specific small interfering RNA (siRNA) was used to knockdown sirtuin-1 (SIRT1) expression. Results: RVT suppressed lipogenesis-related pathway and nuclear factor-kappa B (NF-κB) signaling pathway, decreased the contents of unsaturated fatty acids in SZ95 sebocytes. LA-induced lipogenesis and the expression of lipid-related proteins were all downregulated by RVT. Besides, RVT promoted SIRT1 expression as well as the deacetylation of NF-κB p65 subunit, and subsequently reduced IL-1β and IL-6 secretion under PGN induction. Furthermore, RVT-mediated sebosuppressive and anti-inflammation effects were abolished by pretreatment with AMPK inhibitor Compound C, meanwhile, SIRT1 silencing abrogated the anti-inflammatory capacity of RVT. Conclusions: RVT exhibits sebosuppressive and anti-inflammatory effects in human sebocytes partially via the AMPK pathway, which may justify the role of RVT treatment in acne vulgaris.
2021-05-19 | GSE174601 | GEO
Project description:Homo sapiens cultivar:SZ95 Transcriptome or Gene expression
| PRJNA646337 | ENA
Project description:TRPV3 is highly expressed in human skin and is involved in the development of inflammatory dermatoses. However, it remains unclear whether TRPV3 influences inflammation in human sebaceous glands and its role in the pathogenesis of acne. Here, we showed that TRPV3 expression was increased in the sebaceous glands of facial acne lesions and acne-like mice. TRPV3 increased the secretion of pro-inflammatory cytokines and chemokines in human SZ95 sebocytes, as well as the chemotaxis of neutrophils, which were the major immune cells found in acne lesions. We demonstrated that P.acnes promoted TRPV3 expression through regulating lipid profile especially upregulated arachidonic acid levels in human sebocytes. TRPV3 further upregulated TLR2 expression by promoting transcriptional factor p-FOSL1 expression and its binding to the TLR2 promoter, leading to downstream NF-κB signaling activation. Importantly, either genetic silencing or pharmacological inhibition of TRPV3 alleviated acne-like inflammation in mice, showing reduced acne-characteristic cytokines and chemokines production and neutrophil infiltration by inhibiting the TLR2-NF-κB axis. Thus, our study revealed the critical role of TRPV3 in sebocytes inflammation, which was involved in the development of acne, indicating that TRPV3 is a potential therapeutic target for acne and other disorders of the pilosebaceous unit.
2023-10-13 | GSE245001 | GEO
Project description:Individual acne comedones can undergo spontaneous remission in association with shrunken sebaceous glands (SGs) containing undifferentiated cells under unknown mechanisms. It is also still controversial whether sebum-induced follicular Propionibacterium acnes（P. acnes）interacts with the SGs. We explored the effects of P. acnes and peptidoglycan (PGN) on the aryl hydrocarbon receptor (AhR) activation, lipogenesis and differentiation in cultured human SZ95 sebocytes in vitro. Both formaldehyde-inactivated P. acnes and PGN upregulated mRNA levels of AhR charachteristic downstream genes CYP1A1, CYP1B1, CYP1A2, as well as significantly induced translocation of AhR protein from cytoplasm into nucleus. GSEA revealed pathways of downregulated lipogenesis and upregulated keratinization. In addition, P.acnes and PGN inhibited linoleic acid(LA)-induced neutral lipid synthesis and expressions of Keratin 7 and Mucin1/EMA (sebocyte markers) and increased the expression of Keratin 10 and involucrin (keratinocyte markers), which were abolished after AhR gene silencing. Moreover, inhibited expressions of lipogenesis-related genes such as SREBP1 were observed. In conclusion, we provide evidence that P. acnes can switch sebocytes into a keratinocyte-like differentiation with reduced lipogenesis via AhR, indicating that follicular P. acnes should not only be considered as acnegenic but also as a factor promoting acne remission through feedback regulation of sebum production.
2019-07-16 | GSE134259 | GEO
Project description:Hypoxia regulates cytokine synthesis and lipid droplet-associated protein in SZ95 sebocytes.
| PRJNA454321 | ENA
Project description:Human SZ95 sebocytes were transfected by lipofection with either scramble siRNA or OLR1 siRNA and after 24h were treated with 25µg/ml of UV-oxidized 1-palmitoyl-2-arachidonoyl-sn-phosphocholine (UVPAPC) for 7 hours. Phospholipid oxidation products (OxPL) are versatile stress signaling mediators in the skin. These lipid signaling molecules can be generated non-enzymatically or enzymatically by ultraviolet light, the major extrinsic skin aging factor. OxPL regulate cytoprotective, immunological and metabolic adaptation of the skin to oxidant stress. We here investigated whether the scavenger receptor Oxidized Low Density Lipoprotein Receptor 1 (OLR1, LOX-1) would have a function in cutaneous oxPL signaling. We found that OLR1 is expressed in several cutaneous cell types, most prominently in cells of the sebaceous gland and in keratinocytes. We repressed OLR1 expression with siRNA in SZ95 sebocytes, exposed cells to oxidized 1-palmitoyl-2-arachidonoyl-sn-phosphatiylcholine (PAPC) and performed transcriptomic profiling. Bioinformatic analysis revealed that OxPL exposure induced the Nrf2 antioxidant stress response and aldosterone signaling. The analysis also revealed that OLR1 is not required for the transcriptional regulation induced by oxidized PAPC, but interestingly, OLR1 knockdown affected expression of CNN2, HMRR, ITGB6 and KIF20A, all genes governing cell proliferation and motility. We identify sebocytes as cutaneous cells responsive to lipid mediated redox stress which is not dependent on the scavenger receptor OLR1.
2020-04-15 | GSE98335 | GEO
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:Propionibacterium acnes and peptidoglycan activate aryl hydrocarbon receptor and modify differentiation of SZ95 sebocytes in vitro
| PRJNA554580 | ENA