Lamin A mutations influence Notch signaling and the osteogenic phenotype of human primary mesenchymal cells in a tissue-specific manner

Lamin A is involved in many cellular functions due to its ability to bind chromatin and transcription factors and affect their properties. Mutations of LMNA gene encoding lamin A affect the differentiation capacity of stem cells, but the mechanisms of this influence remain largely unclear. We and others have reported recently an interaction of lamin A with Notch pathway, which is among the main developmental regulators of cellular identity. The aim of this study was to explore the influence of LMNA mutations on the proosteogenic response of human cells of mesenchymal origin and to further explore the interaction of LMNA with Notch pathway. Mutations R527C and R471C in LMNA are associated with mandibuloacral dysplasia type A, a highly penetrant disease with a variety of abnormalities involving bone development. We used lentiviral constructs bearing mutations R527C and R471C and explored its influence on proosteogenic phenotype expression and Notch pathway activity in four types of human cells: umbilical vein endothelial cells (HUVEC), cardiac mesenchymal cells (HCMC), aortic smooth muscle cells (HASMC), and aortic valve interstitial cells (HAVIC). The proosteogenic response of the cells was induced by the addition of either LPS or specific effectors of osteogenic differentiation to the culture medium; phenotype was estimated by the expression of osteogenic markers by qPCR; activation of Notch was assessed by expression of Notch-related and Notch-responsive genes by qPCR and by activation of a luciferase CSL-reporter construct. Overall, we observed different reactivity of all four cell lineages to the stimulation with either LPS or osteogenic factors. R527C had a stronger influence on the proosteogenic phenotype. We observed the inhibiting action of LMNA R527C on osteogenic differentiation in HCMC in the presence of activated Notch signaling, while LMNA R527C caused the activation of osteogenic differentiation in HAVIC in the presence of activated Notch signaling. Our results suggest that the effect of a LMNA mutation is strongly dependent not only on a specific mutation itself, but also might be influenced by the intrinsic molecular context of a cell lineage.

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Hypertension Increases Connexin43 in a Tissue-Specific Manner

Circulation ◽

10.1161/01.cir.95.4.1007 ◽

1997 ◽

Vol 95 (4) ◽

pp. 1007-1014 ◽

Cited By ~ 59

Author(s):

Jacques-Antoine Haefliger ◽

Einar Castillo ◽

Ge´rard Waeber ◽

Gabriela E. Bergonzelli ◽

Jean-Franc¸ois Aubert ◽

...

Keyword(s):

Tissue Specific ◽

Specific Manner

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Tentacle Morphological Variation Coincides with Differential Expression of Toxins in Sea Anemones

Toxins ◽

10.3390/toxins13070452 ◽

2021 ◽

Vol 13 (7) ◽

pp. 452

Author(s):

Lauren M. Ashwood ◽

Michela L. Mitchell ◽

Bruno Madio ◽

David A. Hurwood ◽

Glenn F. King ◽

...

Keyword(s):

Differential Expression ◽

Morphological Variation ◽

Expression Profiles ◽

The Body ◽

Sea Anemones ◽

Tissue Specific ◽

Venom Composition ◽

Specific Manner ◽

Branched Structures ◽

Morphological Variants

Phylum Cnidaria is an ancient venomous group defined by the presence of cnidae, specialised organelles that serve as venom delivery systems. The distribution of cnidae across the body plan is linked to regionalisation of venom production, with tissue-specific venom composition observed in multiple actiniarian species. In this study, we assess whether morphological variants of tentacles are associated with distinct toxin expression profiles and investigate the functional significance of specialised tentacular structures. Using five sea anemone species, we analysed differential expression of toxin-like transcripts and found that expression levels differ significantly across tentacular structures when substantial morphological variation is present. Therefore, the differential expression of toxin genes is associated with morphological variation of tentacular structures in a tissue-specific manner. Furthermore, the unique toxin profile of spherical tentacular structures in families Aliciidae and Thalassianthidae indicate that vesicles and nematospheres may function to protect branched structures that host a large number of photosynthetic symbionts. Thus, hosting zooxanthellae may account for the tentacle-specific toxin expression profiles observed in the current study. Overall, specialised tentacular structures serve unique ecological roles and, in order to fulfil their functions, they possess distinct venom cocktails.

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Syntaxin 1A Gene Is Negatively Regulated in a Cell/Tissue Specific Manner by YY1 Transcription Factor, Which Binds to the −183 to −137 Promoter Region Together with Gene Silencing Factors Including Histone Deacetylase

Biomolecules ◽

10.3390/biom11020146 ◽

2021 ◽

Vol 11 (2) ◽

pp. 146

Author(s):

Takahiro Nakayama ◽

Toshiyuki Fukutomi ◽

Yasuo Terao ◽

Kimio Akagawa

Keyword(s):

Transcription Factor ◽

Gene Silencing ◽

Protein Complex ◽

Promoter Region ◽

Neuronal Cell ◽

Syntaxin 1A ◽

Tissue Specific ◽

Cell Tissue ◽

Specific Manner ◽

A Cell

The HPC-1/syntaxin 1A (Stx1a) gene, which is involved in synaptic transmission and neurodevelopmental disorders, is a TATA-less gene with several transcription start sites. It is activated by the binding of Sp1 and acetylated histone H3 to the −204 to +2 core promoter region (CPR) in neuronal cell/tissue. Furthermore, it is depressed by the association of class 1 histone deacetylases (HDACs) to Stx1a–CPR in non-neuronal cell/tissue. To further clarify the factors characterizing Stx1a gene silencing in non-neuronal cell/tissue not expressing Stx1a, we attempted to identify the promoter region forming DNA–protein complex only in non-neuronal cells. Electrophoresis mobility shift assays (EMSA) demonstrated that the −183 to −137 OL2 promoter region forms DNA–protein complex only in non-neuronal fetal rat skin keratinocyte (FRSK) cells which do not express Stx1a. Furthermore, the Yin-Yang 1 (YY1) transcription factor binds to the −183 to −137 promoter region of Stx1a in FRSK cells, as shown by competitive EMSA and supershift assay. Chromatin immunoprecipitation assay revealed that YY1 in vivo associates to Stx1a–CPR in cell/tissue not expressing Stx1a and that trichostatin A treatment in FRSK cells decreases the high-level association of YY1 to Stx1a-CPR in default. Reporter assay indicated that YY1 negatively regulates Stx1a transcription. Finally, mass spectrometry analysis showed that gene silencing factors, including HDAC1, associate onto the −183 to −137 promoter region together with YY1. The current study is the first to report that Stx1a transcription is negatively regulated in a cell/tissue-specific manner by YY1 transcription factor, which binds to the −183 to −137 promoter region together with gene silencing factors, including HDAC.

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Retinoid nutritional status differently affects the expression of Japanese quail retinoic acid receptor-beta isoform transcripts in a tissue-specific manner

Journal of Endocrinology ◽

10.1677/joe.0.1690281 ◽

2001 ◽

Vol 169 (2) ◽

pp. 281-290 ◽

Cited By ~ 3

Author(s):

ZW Fu ◽

T Kubo ◽

K Sugahara ◽

T Noguchi ◽

H Kato

Keyword(s):

Retinoic Acid ◽

Nutritional Status ◽

Japanese Quail ◽

Retinoic Acid Receptor ◽

Mrna Levels ◽

Tissue Specific ◽

Specific Manner ◽

Lower Magnitude ◽

Lung And Kidney ◽

Receptor Beta

We investigated the effects of vitamin A (VA) nutritional status on the levels of expression of retinoic acid (RA) receptor-beta (RARbeta) gene in the various tissues of Japanese quail. VA deficiency caused a significant decrease in the mRNA levels of brain, liver, heart, lung and kidney RARbeta2/beta4, whereas no change was observed in the level of testis RARbeta2 transcript. In contrast, reduction in the RARbeta1 transcript caused by VA depletion was observed only in the lung, remaining unchanged in the other tissues. The administration of RA to the VA-deficient quail rapidly induced the expression of RARbeta2/beta4 mRNAs in all the tissues examined, but RA increased the expression of RARbeta1 transcript in the liver, heart, lung and kidney at a lower magnitude. RA could not change the expression of the brain RARbeta1 transcript, while it induced the expression of the testis RARbeta1 mRNA in a temporal way. These results clearly indicate that VA nutritional status differently regulates the expression of RARbeta1 and RARbeta2/beta4 transcripts in a tissue-specific manner.

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W1763 Colonic Expression of Claudin-2 Increases in Colitis and Colitis Associated Cancer (Cac) and is Regulated by EGF Receptor Activation in a Tissue Specific Manner

Gastroenterology ◽

10.1016/s0016-5085(10)63383-5 ◽

2010 ◽

Vol 138 (5) ◽

pp. S-735

Author(s):

Rupesh Chaturvedi ◽

Rizwan Ahmad ◽

Mohammad Asim ◽

Kay Washington ◽

Keith T. Wilson ◽

...

Keyword(s):

Egf Receptor ◽

Receptor Activation ◽

Tissue Specific ◽

Specific Manner

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Caloric restriction reprograms fatty acid oxidation in tissue specific manner

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2021.08.041 ◽

2021 ◽

Vol 177 ◽

pp. S57

Author(s):

Volha Mezhnina ◽

Roman V. Kondratov

Keyword(s):

Fatty Acid ◽

Caloric Restriction ◽

Fatty Acid Oxidation ◽

Acid Oxidation ◽

Tissue Specific ◽

Specific Manner

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Two genes encoding the bovine mitochondrial ATP synthase proteolipid specify precursors with different import sequences and are expressed in a tissue-specific manner.

The EMBO Journal ◽

10.1002/j.1460-2075.1985.tb04111.x ◽

1985 ◽

Vol 4 (13A) ◽

pp. 3519-3524 ◽

Cited By ~ 111

Author(s):

N.J. Gay ◽

J.E. Walker

Keyword(s):

Atp Synthase ◽

Tissue Specific ◽

Mitochondrial Atp Synthase ◽

Specific Manner ◽

Genes Encoding

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Lamin A/C Mechanosensor Drives Tumor Cell Aggressiveness and Adhesion on Substrates With Tissue-Specific Elasticity

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.712377 ◽

2021 ◽

Vol 9 ◽

Author(s):

Enrica Urciuoli ◽

Valentina D’Oria ◽

Stefania Petrini ◽

Barbara Peruzzi

Keyword(s):

Tumor Cell ◽

Tumor Cells ◽

Lung Parenchyma ◽

Normal Lung ◽

Lamin A ◽

Osteosarcoma Cell ◽

Adhesion Properties ◽

Tissue Specific ◽

Definition Of ◽

High Level

Besides its structural properties in the nucleoskeleton, Lamin A/C is a mechanosensor protein involved in perceiving the elasticity of the extracellular matrix. In this study we provide evidence about Lamin A/C-mediated regulation of osteosarcoma cell adhesion and spreading on substrates with tissue-specific elasticities. Our working hypothesis is based on the observation that low-aggressive and bone-resident SaOS-2 osteosarcoma cells express high level of Lamin A/C in comparison to highly metastatic, preferentially to the lung, osteosarcoma 143B cells, thereby suggesting a role for Lamin A/C in tumor cell tropism. Specifically, LMNA gene over-expression in 143B cells induced a reduction in tumor cell aggressiveness in comparison to parental cells, with decreased proliferation rate and reduced migration capability. Furthermore, LMNA reintegration into 143B cells changed the adhesion properties of tumor cells, from a preferential tropism toward the 1.5 kPa PDMS substrate (resembling normal lung parenchyma) to the 28 kPa (resembling pre-mineralized bone osteoid matrix). Our study suggests that Lamin A/C expression could be involved in the organ tropism of tumor cells, thereby providing a rationale for further studies focused on the definition of cancer mechanism of metastatization.

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