Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA231777 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We used the myoma model in conjunction with gene expression profiling with microarray data as an efficient tool for high throughput analysis and to screen for differentially expressed genes. Our aim was to identify candidates playing an important role in SLPI and/or MMP-promoted tumor invasion by comparing oral carcinoma Ca9-22 cells, which highly express secretory leukocyte protease inhibitor (SLPI) gene, with SLPI-deficient Ca9-22 cells. In oral carcinoma Ca9-22 and SLPI-deficient Ca9-22 (ÎSLPI) samples, gene expression profiling was performed with the Affymetrix Human Genome U133 Plus 2.0 Array. Two arrays for 2 cell lines were analyzed.
2016-08-22 | E-GEOD-78501 | biostudies-arrayexpress
Project description:We used the myoma model in conjunction with gene expression profiling with microarray data as an efficient tool for high throughput analysis and to screen for differentially expressed genes. Our aim was to identify candidates playing an important role in SLPI and/or MMP-promoted tumor invasion by comparing oral carcinoma Ca9-22 cells, which highly express secretory leukocyte protease inhibitor (SLPI) gene, with SLPI-deficient Ca9-22 cells.
2016-08-22 | GSE78501 | GEO
Project description:Osteoclastic bone resorption and osteoblastic bone formation/replenishment are closely coupled in bone metabolism. Anabolic parathyroid hormone (PTH), which is commonly used for treating osteoporosis, shifts the balance from osteoclastic to osteoblastic, although the mechanisms underlying this phenomenon are unclear. Here we identified a serine protease inhibitor, secretory leukocyte protease inhibitor (SLPI), as a novel coupling factor that is involved in the PTH-mediated shift to the osteoblastic phase. SLPI was highly upregulated in osteoblasts by PTH, and genetic ablation of SLPI severely impaired PTH-induced bone formation. SLPI induction in osteoblasts enhanced osteoblast differentiation intracellularly and was also secreted extracellularly, attracting neighboring osteoclasts to suppress osteoclastic function. Intravital bone imaging revealed that the PTH-mediated association between osteoblasts and osteoclasts was disrupted in the absence of SLPI. Collectively, these results demonstrate that SLPI, a previously unrecognized bone-coupling factor, mediates the communication of osteoblasts with osteoclasts to promote PTH-induced bone formation.
2021-01-17 | GSE145462 | GEO
Project description:Directed differentiation of stem cells toward chondrogenesis in vitro and in situ to regenerate cartilage suffers from off-target differentiation and hypertrophic tendency. Here, we generated a cartilaginous organoid system from human expanded pluripotent stem cells (hEPSCs) carrying a COL2A1mCherry and COL10A1eGFP double reporter, enabling real-time monitoring of chondrogenesis and hypertrophy. After screening 2,040 FDA-approved drugs, we found that α-adrenergic receptor (α-AR) antagonists, especially phentolamine, stimulated chondrogenesis but repressed hypertrophy, while α2-AR agonists reduced chondrogenesis and induced hypertrophy. Phentolamine prevented cartilage degeneration in hEPSC cartilaginous organoid and human cartilage explant models and stimulated microfracture-activated endogenous skeletal stem cells toward hyaline-like cartilage regeneration without fibrotic degeneration in situ. Mechanistically, α2-AR signaling induced hypertrophic degeneration via cyclic guanosine monophosphate (cGMP)-dependent secretory leukocyte protease inhibitor (SLPI) production. SLPI-deleted cartilaginous organoid was degeneration resistant, facilitating large cartilage defect healing. Ultimately, targeting α2-AR/SLPI was a promising and clinically feasible strategy to regenerate cartilage via promoting chondrogenesis and repressing hypertrophy.
2024-09-30 | GSE249229 | GEO
Project description:Directed differentiation of stem cells toward chondrogenesis in vitro and in situ to regenerate cartilage suffers from off-target differentiation and hypertrophic tendency. Here, we generated a cartilaginous organoid system from human expanded pluripotent stem cells (hEPSCs) carrying a COL2A1mCherry and COL10A1eGFP double reporter, enabling real-time monitoring of chondrogenesis and hypertrophy. After screening 2,040 FDA-approved drugs, we found that α-adrenergic receptor (α-AR) antagonists, especially phentolamine, stimulated chondrogenesis but repressed hypertrophy, while α2-AR agonists reduced chondrogenesis and induced hypertrophy. Phentolamine prevented cartilage degeneration in hEPSC cartilaginous organoid and human cartilage explant models and stimulated microfracture-activated endogenous skeletal stem cells toward hyaline-like cartilage regeneration without fibrotic degeneration in situ. Mechanistically, α2-AR signaling induced hypertrophic degeneration via cyclic guanosine monophosphate (cGMP)-dependent secretory leukocyte protease inhibitor (SLPI) production. SLPI-deleted cartilaginous organoid was degeneration resistant, facilitating large cartilage defect healing. Ultimately, targeting α2-AR/SLPI was a promising and clinically feasible strategy to regenerate cartilage via promoting chondrogenesis and repressing hypertrophy.
2024-09-30 | GSE271814 | GEO
Project description:Secretory Leukocyte Protease Inhibitor Protects Against Severe Urinary Tract Infection in Mice
| PRJEB66138 | ENA
Project description:Tubulointerstitial injury plays an important role in diabetic nephropathy (DN) progression; however, no reliable urinary molecule has been used to predict tubulointerstitial injury and renal outcome of DN clinically. In this study, based on tubulointerstitial transcriptome, we identified secretory leukocyte peptidase inhibitor (SLPI) as the molecule associated with renal fibrosis and prognosis of DN. In tubular cells, high glucose could upregulate SLPI, which bound with β-catenin and GSK-3β reciprocally, abolished the interaction between β-catenin and GSK-3β, diminished GSK-3β-regulated β-catenin phosphorylation and the subsequent ubiquitination and degradation, thus led to β-catenin signaling activation and renal fibrosis. Db/db mice injected with adenovirus carrying Slpi-3xflag-GFP (Ad-Slpi-GFP) developed β-catenin signaling activation in the proximal tubule, worse albuminuria and tubulointerstitial fibrosis. Conversely, Slpi knockout (KO) mice with STZ-induced DN developed less albuminuria, tubulointerstitial fibrosis and β-catenin signaling activation. Furthermore, clinical studies showed that urinary SLPI protein level (uSLPI/Cr) had significant correlation with intrarenal SLPI mRNA and interstitial fibrosis. In an independent prospective cohort enrolled 711 patients with biopsy proven DN, uSLPI/Cr level was significantly associated with eGFR slope and improved the prediction value of renal outcome. Together, our study identified SLPI as a novel critical regulator for the progression of tubulointerstitial injury, which may be used as an independent risk predictor of DN progression.
2022-08-03 | GSE158230 | GEO
Project description:Secretory Leukocyte Peptidase Inhibitor (SLPI) is a Novel Predictor of Tubulointerstitial Injury and Renal Outcome in Patients with Diabetic Nephropathy
| PRJNA664391 | ENA
Project description:Asherman’s Syndrome is characterized by intrauterine adhesions or scarring, which cause infertility, menstrual abnormalities, and recurrent pregnancy loss. The pathophysiology of this syndrome remains unknown, with treatment restricted to recurrent surgical removal of intrauterine scarring, which has limited success. Here, we decode the Asherman’s Syndrome endometrial cell niche by analyzing data from over 200,000 cells with single-cell RNA-sequencing in patients with this condition and through in vitro analyses of Asherman’s Syndrome patient-derived endometrial organoids. Our endometrial atlas highlights the loss of the endometrial epithelium, alterations to epithelial differentiation signaling pathways such as Wnt and Notch, and the appearance of characteristic epithelium expressing secretory leukocyte protease inhibitor during the window of implantation. We describe syndrome-associated alterations in cell-to-cell communication and gene expression profiles that support a dysfunctional pro-fibrotic, pro-inflammatory, and anti-angiogenic environment.
2023-08-03 | GSE216748 | GEO
Project description:Asherman’s Syndrome is characterized by intrauterine adhesions or scarring, which cause infertility, menstrual abnormalities, and recurrent pregnancy loss. The pathophysiology of this syndrome remains unknown, with treatment restricted to recurrent surgical removal of intrauterine scarring, which has limited success. Here, we decode the Asherman’s Syndrome endometrial cell niche by analyzing data from over 200,000 cells with single-cell RNA-sequencing in patients with this condition and through in vitro analyses of Asherman’s Syndrome patient-derived endometrial organoids. Our endometrial atlas highlights the loss of the endometrial epithelium, alterations to epithelial differentiation signaling pathways such as Wnt and Notch, and the appearance of characteristic epithelium expressing secretory leukocyte protease inhibitor during the window of implantation. We describe syndrome-associated alterations in cell-to-cell communication and gene expression profiles that support a dysfunctional pro-fibrotic, pro-inflammatory, and anti-angiogenic environment.
2023-08-03 | GSE215968 | GEO