Similar Datasets
Project description:To study and correlate modulations of miRNome with modifications of transcriptome in human stress-induced senescent fibroblasts, Agilent microarrays data were compared by bioinformatics analysis with a focus on ECM components. We identified two unreported direct interactions since we highlighted a reduction in the expression of both miR-22-5p and -199a-5p in senescent fibroblasts, correlated to an increase of MMP1 expression.
2022-01-09 | GSE77406 | GEO
Project description:To study and correlate modulations of miRNome with modifications of transcriptome in human stress-induced senescent fibroblasts, Agilent microarrays data were compared by bioinformatics analysis with a focus on ECM components. We identified two unreported direct interactions since we highlighted a reduction in the expression of both miR-22-5p and -199a-5p in senescent fibroblasts, correlated to an increase of MMP1 expression.
2022-01-09 | GSE77074 | GEO
Project description:Identification of new microRNA-22-5p and -199a-5p/MMP1 functional interactions in stress-induced senescent human dermal fibroblasts
| PRJNA310229 | ENA
Project description: Not available
| S-EPMC10325758 | biostudies-literature
Project description:Accumulation of senescent dermal fibroblasts drives skin aging. The reactivation of proliferation is one strategy to modulate cell senescence. Recently, we reported the exact chemical composition of the hydrophilic extract of Oenothera biennis cell cultures (ObHEx) and we showed its skin anti-aging properties. The aim of this work is to assess its biological effect specifically on cell senescence. ObHEx action has been evaluated on normal human dermal fibroblasts subjected to stress-induced premature senescence (SIPS) through an ultra-deep proteomic analysis, leading to the most global senescence-associated proteome so far. Mass spectrometry data show that the treatment with ObHEx re-establishes levels of crucial mitotic proteins, strongly downregulated in senescent cells. To validate our proteomics findings, we proved that ObHEx can, in part, restore the activity of 'senescence-associated-ß-galactosidase', the most common hallmark of senescent cells. Furthermore, to assess if the upregulation of mitotic protein levels translates into a cell cycle re-entry, FACS experiments have been carried out, demonstrating a small but significative reactivation of senescent cell proliferation by ObHEx. In conclusion, the deep senescence-associated global proteome profiling published here provides a panel of hundreds of proteins deregulated by SIPS that can be used by the community to further understand senescence and the effect of new potential modulators. Moreover, proteomics analysis pointed to a specific promitotic effect of ObHEx on senescent cells. Thus, we suggest ObHEx as a powerful adjuvant against senescence associated with skin aging.
| S-EPMC9735661 | biostudies-literature
Project description:The skin is a multilayered and primary defensive organ. Intimate intercellular communication in the skin is necessary to ensure effective surveillance. Extracellular vesicles (EVs) are being explored for their involvement in intercellular skin communication. The aim of this study was to evaluate how human dermal fibroblasts (HDFs) accelerate EV production during senescence and the effects of senescence-associated EVs on epidermal homeostasis. Replicative senescent HDFs were assessed with senescence-associated ?-galactosidase staining and the expression of senescence-related markers. Isolated EVs were characterized by dynamic light scattering and EV marker expression. EVs secreted from untreated young or senescent HDFs, or from those treated with a nSMase inhibitor, antioxidant, and lysosomal activity regulators, were determined by sandwich ELISA for CD81. Human epidermal keratinocytes were treated with young- and senescent HDF-derived EVs. Compared to young HDFs, senescent HDFs produced relatively high levels of EVs due to the increased nSMase activity, oxidative stress, and altered lysosomal activity. The nSMase inhibitor, antioxidant, and agents that recovered lysosomal activity reduced EV secretion in senescent HDFs. Relative to young HDF-derived EVs, senescent HDF-derived EVs were less supportive in keratinocyte differentiation and barrier function but increased proinflammatory cytokine IL-6 levels. Our study suggests that dermis-derived EVs may regulate epidermal homeostasis by reflecting cellular status, which provides insight as to how the dermis communicates with the epidermis and influences skin senescence.
| S-EPMC7037765 | biostudies-literature
Project description:Both SIRT1 and UVA radiation are involved in cellular damage processes such as apoptosis, senescence and ageing. MicroRNAs (miRNAs) have been reported to be closely related to UV radiation, as well as to SIRT1. In this study, we investigated the connections among SIRT1, UVA and miRNA in human skin primary fibroblasts. Our results showed that UVA altered the protein level of SIRT1 in a time point-dependent manner. Using miRNA microarray, bioinformatics analysis, we found that knocking down SIRT1 could cause up-regulation of miR-27a-5p and the latter could down-regulate SMAD2, and these results were verified by qRT-PCR or Western blot. Furthermore, UVA radiation (5 J/cm2 ), knocking down SIRT1 or overexpression of miR-27a-5p led to increased expression of MMP1, and decreased expressions of COL1 and BCL2. We also found additive impacts on MMP1, COL1 and BCL2 under the combination of UVA radiation + Sirtinol (SIRT1 inhibitor), or UVA radiation + miR-27a-5p mimic. SIRT1 activator resveratrol could reverse damage changes caused by UVA radiation. Besides, absent of SIRT1 or overexpression of miR-27a-5p increased cell apoptosis and induced cell arrest in G2/M phase. Taken together, these results demonstrated that UVA could influence a novel SIRT1-miR-27a-5p-SMAD2-MMP1/COL1/BCL2 axis in skin primary fibroblasts, and may provide potential therapeutic targets for UVA-induced skin damage.
| S-EPMC7520305 | biostudies-literature
Project description:Herbal medicines are attractive agents for human care. In this study, we found that the alcohol extract of Ajuga taiwanensis (ATE) screened from a chemical bank exhibited potent capacity for suppressing senescence associated biomarkers, including SA-β-gal and up-regulated p53 in old human dermal fibroblasts (HDFs) without induction of significant cytotoxicity up to 100 µg/ml. Concomitantly, cells re-entered the cell cycle by reducing G1 phase arrest and increasing cell growth rate. The ATE was further partitioned to obtain the sub-fractions of n-butanol (BuOH), ethyl acetate (EA) and water. The BuOH and water sub-fractions exhibited less effects on prohibition of cell growth than the EA sub-fraction. All of these sub-fractions exhibited the ability on suppressing SA-β-gal and p53 of old HDFs as low as 5-10 µg/ml. Under the activity guided fractionation and isolation, a major active constituent named AT-1 was isolated. The AT-1 was further identified as 8-O-acetylharpagide by structural analysis, and it could suppress SA-β-gal and p53 of old HDFs below 10 µM. In addition, the intracellular reactive oxygen species (ROS) levels of old HDFs were suppressed by ATE, the sub-fractions of BuOH and water, and AT-1. However, the EA sub-fraction showed little ability on suppression of ROS. Furthermore, we performed an in vivo study using aging mice to be fed with ATE and the sub-fractions followed by immunohistochemical (IHC) staining. The expression of p53 and SA-β-gal was significantly reduced in several tissue sections, including skin, liver, kidney, and spleen. Taken together, current data demonstrated that A. taiwanensis could suppress cellular senescence in HDFs, and might be used for health care.
| S-EPMC7661503 | biostudies-literature
Project description:Aging is associated with a decrease of extracellular matrix and an increase of senescent cells in the dermal layer. Here, to examine whether and how senescent cells are involved in aging-related deterioration of the dermal layer, we cocultured dermal young fibroblasts (low-passage number) with senescent cells (high-passage number) in Transwells, in which the two cell types are separated by a semipermeable membrane. Young fibroblasts in coculture showed decreased collagen type I alpha 1 chain and elastin gene expression, and increased matrix metalloproteinase 1 (MMP1) gene expression. To identify causative factors, we compared gene expression of young and senescent cells and selected candidate secretory factors whose expression was increased by ?2.5 in senescent fibroblasts. Then, we used siRNAs to knock down each of the 11 candidate genes in senescent fibroblasts in the coculture system. Knockdown of complement factor D (CFD) in senescent fibroblasts significantly reduced the increase of MMP1 in the cocultured young fibroblasts. In monocultures, treatment of young fibroblasts with CFD resulted in increased MMP1 gene expression, while knockdown of CFD in senescent fibroblasts decreased MMP1 gene expression. In addition, production of CFD was increased in culture medium of untreated senescent fibroblasts. Furthermore, CFD gene and protein expression were increased in the dermal layer of skin specimens from aged subjects (>70?years old), compared to young subjects (<20?years old). Overall, these results suggest that senescent cells negatively influence matrix production and promote degradation of nearby fibroblasts in the dermal layer, in part through secretion of CFD.
| S-EPMC6850482 | biostudies-literature
Project description:BackgroundNeonatal sepsis is a serious condition. Recent clinical studies have indicated that microRNAs (miRNAs) are key players in the pathogenesis of sepsis, which could be used as biomarkers for this condition.Patients and methodsA total of 90 neonates with sepsis and 90 healthy neonates were enrolled in this study. qRT-PCR was performed to measure the expression levels of serum miR-34a-5p and miR-199a-3p.ResultsmiR-34a-5p and miR-199a-3p serum levels were significantly reduced in neonates with sepsis compared with those in healthy neonates (P = 0.006 and P = 0.001, respectively). Significant correlations of miR-34a-5p and miR-199a-3p with each of TLC, RDW, RBS, and C-reactive protein (CRP) as well as SNAPII were observed, indicating their associations with the severity of neonatal sepsis.ConclusionmiR-34a-5p and miR-199a-3p may be useful as novel biomarkers in neonatal sepsis and may provide a new direction for its treatment.
| S-EPMC8735601 | biostudies-literature