scholarly journals GPR30 Promotes Prostate Stromal Cell Activation via Suppression of ERα Expression and Its Downstream Signaling Pathway

Endocrinology ◽  
2016 ◽  
Vol 157 (8) ◽  
pp. 3023-3035 ◽  
Author(s):  
Bona Jia ◽  
Yu Gao ◽  
Mingming Li ◽  
Jiandang Shi ◽  
Yanfei Peng ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Signaling Pathway ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Cell Activation ◽  
Vital Role ◽  
Stem Cell Marker ◽  
Cell Phenotype ◽  
Differentiation Markers ◽  
And Migration

Cancer-associated fibroblasts (CAFs) play a vital role in malignant transformation and progression of prostate cancer (PCa), and accumulating evidence suggests an enhancing effect of estrogens on PCa. The present study aimed to investigate the possible origin of prostate CAFs and the effects of estrogen receptors, G protein-coupled receptor 30 (GPR30) and estrogen receptor (ER)-α, on stromal cell activation. High expression of fibroblast activation protein (FAP), CD44, and nonmuscle myosin heavy chain B (SMemb) accompanied by low expression of smooth muscle differentiation markers was found in the stromal cells of PCa tissues and in cultured human prostate CAFs. Additionally, SMemb expression, which is coupled to cell phenotype switching and proliferation, was coexpressed with FAP, a marker of activated stromal cells, and with the stem cell marker CD44 in the stromal cells of PCa tissue. Prostate CAFs showed high GPR30 and low ERα expression. Moreover, GPR30 was coexpressed with FAP, CD44, and SMemb. Furthermore, the study demonstrated that the overexpression of GPR30 or the knockdown of ERα in prostate stromal cells induced the up-regulation of FAP, CD44, Smemb, and the down-regulation of smooth muscle markers. The conditioned medium from these cells promoted the proliferation and migration of LNCaP and PC3 PCa cells. GPR30 knockdown or ERα overexpression showed opposite effects. Finally, we present a novel mechanism whereby GPR30 limits ERα expression via inhibition of the cAMP/protein kinase A signaling pathway. These results suggest that stem-like cells within the stroma are a possible source of prostate CAFs and that the negative regulation of ERα expression by GPR30 is centrally involved in prostate stromal cell activation.

scholarly journals Scopoletin inhibits PDGF-BB-induced proliferation and migration of airway smooth muscle cells by regulating NF-κκB signaling pathway

2022 ◽  
Vol 50 (1) ◽  
pp. 92-98
Author(s):  
Zhongxiang Fan ◽  
Dan Tang ◽  
Qiang Wu ◽  
Qun Huang ◽  
Jie Song ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Airway Smooth Muscle ◽  
Airway Remodeling ◽  
Muscle Cells ◽  
Chronic Inflammatory Disease ◽  
Migration And Invasion ◽  
Airway Smooth Muscle Cells ◽  
And Migration

Background: Asthma is a common chronic inflammatory disease of the airway, and airway remodeling and the proliferation mechanism of airway smooth muscle cells (ASMCs) is of great significance to combat this disease.Objective: To assess possible effects of scopoletin on asthma and the potential signaling pathway.Materials and methods: ASMCs were treated PDGF-BB and scopoletin and subjected to cell viability detection by CCK-8 assay. Cell migration of ASMCs was determined by a wound closure assay and transwell assay. The protein level of MMP2, MMP9, calponin and α-SMA were measured using western blot. The levels of NF-κB signaling pathway were detected by Western blotting.Results: Scopoletin inhibited proliferation of PDGF-BB - induced ASMCs. Also it suppressed the migration and invasion of PDGF-BB - induced ASMCs. We further showed that Scopoletin regulated phenotypic transition of ASMCs. Mechanically, Scopoletin inhibited proliferation and invasion of ASMCs by regulating NF-κB signaling pathway.Conclusions: We therefore thought Scopoletin could serve as a promising drug for the treatment of asthma.

CEMIP regulates the proliferation and migration of vascular smooth muscle cells in atherosclerosis through the WNT–beta-catenin signaling pathway

2020 ◽  
Vol 98 (2) ◽  
pp. 249-257
Author(s):  
Qiang Xue ◽  
Xiaoli Wang ◽  
Xiaohui Deng ◽  
Yue Huang ◽  
Wei Tian
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Matrix Metalloproteinase ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
And Migration ◽  
Proliferation And Migration

In this study we investigated the regulatory role of cell-migration-inducing and hyaluronan-binding protein (CEMIP) in the proliferation and migration of vascular smooth muscle cells (VSMCs). The mRNA and protein levels of CEMIP were upregulated in the plasma samples from patients with atherosclerosis, and in VSMCs stimulated with platelet-derived growth factor-BB (PDGF-BB), compared with plasma from healthy subjects and untreated VSMCs. Silencing CEMIP suppressed PDGF-BB-induced cell migration and proliferation in VSMCs, as determined using a Cell Counting Kit-8 assays, 5-ethynyl-2′-deocyuridine (EDU) assays, flow cytometry, wound healing assays, and Transwell assays. Overexpression of CEMIP promoted the proliferation and migration of VSMCs via activation of the Wnt–β-catenin signaling pathway and the upregulation of its target genes, including matrix metalloproteinase-2, matrix metalloproteinase-7, cyclin D1, and c-myc, whereas CEMIP deficiency showed the opposite effects. The knockdown of CEMIP in ApoE−/− mice by intravenous injection of lentiviral vector expressing si-CEMIP protected against high-fat-diet-induced atherosclerosis, as shown by the reduced aortic lesion areas, aortic sinus lesion areas, and the concentration of blood lipids compared with mice normally expressing CEMIP. These results demonstrated that CEMIP regulates the proliferation and migration of VSMCs in atherosclerosis by activating the WNT–β-catenin signaling pathway, which suggests the therapeutic potential of CEMIP for the management of atherosclerosis.

scholarly journals Analysis of Transcriptomic Changes in Bovine Endometrial Stromal Cells Treated With Lipopolysaccharide

2020 ◽  
Vol 7 ◽  
Author(s):  
Xuefen Ding ◽  
Haimiao Lv ◽  
Lixin Deng ◽  
Wenju Hu ◽  
Zhan Peng ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Stromal Cells ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Interleukin 1 ◽  
Interleukin 12 ◽  
Receptor Interaction ◽  
Control Group ◽  
Toll Like Receptor ◽  
Endometrial Stromal Cells

Endometritis adversely affects the ability of cattle to reproduce and significantly reduces milk production. The is mainly composed of epithelial and stromal cells, and they produce the first immune response to invading pathogens. However, most of the epithelial cells are disrupted, and stromal cells are exposed to an inflammatory environment when endometritis occurs, especially postpartum. Many bacteria and toxins start attacking stromal cell due to loss of epithelium, which stimulates Toll-like receptor (TLRs) on stromal cells and causes upregulated expression of cytokines. Understanding the genome-wide characterization of bovine endometritis will be beneficial for prevention and treatment of endometritis. In this study, whole-transcriptomic gene changes in bovine endometrial stromal cells (BESCs) treated with LPS were compared with those treated with PBS (control group) and were analyzed by RNA sequencing. Compared with the control group, a total of 366 differentially expressed genes (DEGs) were identified in the LPS-induced group (234 upregulated and 132 downregulated genes), with an adjusted P < 0.05 by DESeq. Gene Ontology (GO) enrichment analysis revealed that DEGs were most enriched in interleukin-1 receptor binding, regulation of cell activation, and lymphocyte-activated interleukin-12 production. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed DEGs were most enriched in the TNF signaling pathway, Toll-like receptor signaling pathway, cytokine–cytokine receptor interaction, NF-κB signaling pathway, and chemokine signaling pathway. The results of this study unraveled BESCs affected with LPS transcriptome profile alterations, which may have a significant effect on treatment inflammation by comprehending molecular mechanisms and authenticating unique genes related to endometritis.

The Hematopoietic Supportive Function of Adult Bone Marrow Mesenchymal Stem Cells Is Lost after Differentiation Induction towards Adipocytic, Osteoblastic and Vascular Smooth Muscle Lineages

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4742-4742
Author(s):  
Tatiana Ribeiro ◽  
Aurelie Picard ◽  
Elfi Ducrocq ◽  
Alain Langonne ◽  
Philippe Rosset ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Stromal Cells ◽  
Expansion Medium ◽  
Hsc Niche ◽  
And Migration

Abstract The bone marrow (BM) hematopoietic stem cell (HSC) niche is a specialized structure of the microenvironment, which supports survival and regulates HSC function (i.e. the HSC control of the self-renewal/differentiation balance and migration). The supportive cells involved in the HSC niche are usually named as “stromal cells” but their precise nature remains a matter of debate (in particular, to know whether these cells belong to osteoblastic or to vascular smooth muscle lineage). Mesenchymal stem cells (MSCs) that are present into the BM are characterized by a broad differentiation potential including adipocytic (A), osteoblastic (O) and vascular smooth muscle (V) pathways. Although MSCs are believed to be at the origin of stromal cells, their real function within the niche is unknown. The aim of this study was to investigate in vitro the hematopoietic function (HSC support and migration) of cultured adult BM MSCs non-differentiated and during induced differentiation along A, O and V lineages. MSCs were obtained from BM nucleated cells of patients undergoing orthopedic surgery by culture in expansion medium (alpha-MEM medium with 10% FCS and 1 ng/mL FGF-2). The MSCs were tested before (cultured in expansion medium) and during differentiation induction in appropriate medium for A, O or V lineages (from 3 to 21 days). Interestingly, non-differentiated MSCs already co-expressed O (PTH-receptor), A (leptin) and V (ASMA) markers as assessed by Western blotting. Capacity of MSCs to support hematopoiesis was evaluated by long-term cultures (for 5 wks) with BM CD34+ cells in limiting dilution (CAFC assay), and capacity to control CD34+ cell migration by using Transwells seeded with MSCs (trans-stromal migration assay). We showed that non-differentiated MSCs have the most important capacity to support hematopoiesis (5-week CAFC frequency) and that this capacity was quickly and dramatically lost from 3 days of differentiation towards A (36±2% of non-differentiated values), O (40±3%) and V (38±1%) lineages. This capacity was almost abolished after 14 days of A, O and V differentiation (<5%). In parallel, CD34+ cell migration was clearly reduced through 3-day A and O differentiated MSCs, while it was increased through 3-day V differentiated MSCs (5 fold). These results show that MSCs maintained in vitro in non-differentiated state (although already expressing some A, O and V markers), display the strongest hematopoietic supportive activity compared to MSCs induced to differentiate into adipocytic, osteoblastic, or vascular smooth muscle lineages. Therefore, the stromal cell function could be supported by a cell close to a non-differentiated MSC in endosteal or perivascular niches as well. In contrast, vascular smooth muscle differentiated MSCs at advanced stages could be devoted rather to HSC migration control than to HSC support.

MT1-MMP Plays a Critical Role in Hematopoiesis by Regulating HIF-Mediated Chemo-/Cytokine Gene Transcription within Niche Cells.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2351-2351
Author(s):  
Chiemi Nishida ◽  
Kaori Sato-Kusubata ◽  
Yoshihiko Tashiro ◽  
Ismael Gritli ◽  
Aki Sato ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Gene Transcription ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Stem Cell Differentiation ◽  
Cell Phenotype ◽  
Hematopoietic Stem

Abstract Abstract 2351 Stem cells reside in a physical niche. The organization of cellular niches has been shown to play a key role in regulating normal stem cell differentiation, stem cell maintenance and regeneration. Various stem cell niches have been shown to be hypoxic, thereby maintaining the stem cell phenotype of e.g. hematopoietic stem cells (HSCs) or cancer stem cells. The bone marrow (BM) niche is a rich reservoir of tissue-specific pluripotent HSCs. Proteases such as matrix metalloproteinases (MMPs) have been implicated in cell movement, partly due to their proteolytic function, and they have been linked to cellular processes such as cell proliferation and differentiation. The proteolytic function of Membrane-type 1 MMP (MT1-MMP/MMP-14) is essential for angiogenesis, arthritis and tumour growth. Recently, it has been reported that MT1-MMP is highly expressed in HSCs and stromal/niche cells. However the clear function of MT1-MMP in hematopoiesis is not well understood. To reveal the functional consequences of MT1-MMP deficiency for post-natal hematopoiesis in vivo, we have taken advantage of MT1-MMP−/− mice to demonstrate that MT1-MMP deficiency leads to impaired steady state hematopoiesis of all hematopoietic cell lineages. In a search for factors whose deficiency could cause this hematopoietic phenotype, we found not only reduced protein release, but also reduced transcription of the following growth factors/chemokines in MT1-MMP−/− mice: erythropoietin (Epo), stromal cell-derived factor-1 (SDF-1a/CXCL12), interleukin-7 (IL-7) and Kit ligand (KitL, also known as stem cell factor). All of these factors, except for Epo, are typical stromal cell-derived factors. To ensure that impaired gene transcription in vivo was not due to a lower number of stromal cells in vivo, we demonstrated that MT1-MMP knockdown in stromal cells in vitro also reduced transcription of the stromal cell derived factors SDF-1a/CXCL12, IL-7 and KitL. In contrast, overexpression of MT1-MMP in stromal cells enhanced gene transcription of these factors. All genes, whose transcription was altered in vitro and in vivo due to MT1-MMP deficiency, had one thing in common: their gene transcription is regulated by the hypoxia inducible factor-1 (HIF-1) pathway. Further mechanistic studies revealed that MT1-MMP activates the HIF-1 pathway via factor inhibiting HIF-1 (FIH-1) within niche cells, thereby inducing the transcription of HIF-responsive genes, which induce terminal hematopoietic differentiation. Thus, MT1-MMP in niche cells regulates postnatal hematopoiesis by modulating hematopoietic HIF-dependent niche factors that are critical for terminal differentiation and migration. Disclosures: No relevant conflicts of interest to declare.

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