5 results on '"Tasneem Shinwari"'
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2. Convergence of TGFβ and BMP signaling in regulating human bone marrow stromal cell differentiation
- Author
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Mona Elsafadi, Tasneem Shinwari, Sami Al-Malki, Muthurangan Manikandan, Amer Mahmood, Abdullah Aldahmash, Musaad Alfayez, Moustapha Kassem, and Nehad M. Alajez
- Subjects
Medicine ,Science - Abstract
Abstract Targeting regulatory signaling pathways that control human bone marrow stromal (skeletal or mesenchymal) stem cell (hBMSC) differentiation and lineage fate determination is gaining momentum in the regenerative medicine field. Therefore, to identify the central regulatory mechanism of osteoblast differentiation of hBMSCs, the molecular phenotypes of two clonal hBMSC lines exhibiting opposite in vivo phenotypes, namely, bone forming (hBMSC+bone) and non-bone forming (hBMSC−Bone) cells, were studied. Global transcriptome analysis revealed significant downregulation of several TGFβ responsive genes, namely, TAGLN, TMP1, ACTA2, TGFβ2, SMAD6, SMAD9, BMP2, and BMP4 in hBMSC−Bone cells and upregulation on SERPINB2 and NOG. Transcriptomic data was associated with marked reduction in SMAD2 protein phosphorylation, which thereby implies the inactivation of TGFβ and BMP signaling in those cells. Concordantly, activation of TGFβ signaling in hBMSC−Bone cells using either recombinant TGFβ1 protein or knockdown of SERPINB2 TGFβ-responsive gene partially restored their osteoblastic differentiation potential. Similarly, the activation of BMP signaling using exogenous BMP4 or via siRNA-mediated knockdown of NOG partially restored the differentiation phenotype of hBMSC−Bone cells. Concordantly, recombinant NOG impaired ex vivo osteoblastic differentiation of hBMSC+Bone cells, which was associated with SERBINB2 upregulation. Our data suggests the existence of reciprocal relationship between TGFB and BMP signaling that regulates hBMSC lineage commitment and differentiation, whilst provide a plausible strategy for generating osteoblastic committed cells from hBMSCs for clinical applications. more...
- Published
- 2019
- Full Text
- View/download PDF
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3. Transgelin is a poor prognostic factor associated with advanced colorectal cancer (CRC) stage promoting tumor growth and migration in a TGFβ-dependent manner
- Author
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Tasneem Shinwari, Mona Elsafadi, Nehad M. Alajez, Mohammad Mobarak, Radhakrishnan Vishnubalaji, Muthurangan Manikandan, Moustapha Kassem, Abdullah Aldahmash, Amer Mahmood, Musaad Alfayez, and Sami Almalki more...
- Subjects
Cancer Research ,Angiogenesis ,Colorectal cancer ,medicine.medical_treatment ,Immunology ,Mice, Nude ,Muscle Proteins ,Biology ,p38 Mitogen-Activated Protein Kinases ,Actin cytoskeleton organization ,Article ,Targeted therapy ,Transforming Growth Factor beta1 ,Cellular and Molecular Neuroscience ,Cell growth ,Cell Movement ,Databases, Genetic ,medicine ,Animals ,Humans ,Gene Regulatory Networks ,Neoplasm Invasiveness ,lcsh:QH573-671 ,Cell Proliferation ,Neoplasm Staging ,lcsh:Cytology ,Microfilament Proteins ,Cell migration ,Cell Biology ,medicine.disease ,HCT116 Cells ,Tumor Burden ,Colon cancer ,Gene Expression Regulation, Neoplastic ,Tumor progression ,Cancer cell ,Cancer research ,Female ,Colorectal Neoplasms ,HT29 Cells ,Transforming growth factor ,Signal Transduction - Abstract
Colorectal cancer (CRC) is the fourth most common cancer type globally. Investigating the signaling pathways that maintain cancer cell phenotype can identify new biomarkers for targeted therapy. Aberrant transforming growth factor-β (TGFβ) signaling has been implicated in CRC progression, however, the exact mechanism by which TGFβ exerts its function is still being unraveled. Herein, we investigated TAGLN expression, prognostic value, and its regulation by TGFβ in CRC. While TAGLN was generally found to be downregulated in CRC, elevated expression of TAGLN was associated with advanced CRC stage and predicted poor overall survival (hazard ratio (HR) = 1.8, log-rank test P-value = 0.014) and disease-free survival (HR = 1.6, log-rank test P-value = 0.046), hence implicating TAGLN as poor prognostic factor in CRC. Forced expression of TAGLN was associated with enhanced CRC cell proliferation, clonogenic growth, cell migration and in vivo tumor formation in immunocompromised mice, while targeted depletion of TAGLN exhibited opposing biological effects. Global gene expression profiling of TAGLN-overexpressing or TAGLN-deficient CRC cell lines revealed deregulation of multiple cancer-related genes and signaling pathways. Transmission electron microscopy (TEM) revealed ultrastructural changes due to loss of TAGLN, including disruption of actin cytoskeleton organization and aberrant actin filament distribution. Hierarchical clustering, principle component, and ingenuity pathway analyses revealed distinct molecular profile associated with TAGLNhigh CRC patients with remarkable activation of a number of mechanistic networks, including SMARCA4, TGFβ1, and P38 MAPK. The P38 MAPK was the top predicted upstream regulator network promoting cell movement through regulation of several intermediate molecules, including TGFβ1. Concordantly, functional categories associated with cellular movement and angiogenesis were also enriched in TAGLNhigh CRC, supporting a model for the molecular mechanisms linking TGFβ-induced upregulation of TAGLN and CRC tumor progression and suggesting TAGLN as potential prognostic marker associated with advanced CRC pathological stage. more...
- Published
- 2020
- Full Text
- View/download PDF
4. Convergence of TGFβ and BMP signaling in regulating human bone marrow stromal cell differentiation
- Author
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Amer Mahmood, Nehad M. Alajez, Muthurangan Manikandan, Tasneem Shinwari, Sami Almalki, Mona Elsafadi, Moustapha Kassem, Musaad Alfayez, and Abdullah Aldahmash
- Subjects
Stromal cell ,Science ,Down-Regulation ,Bone Morphogenetic Protein 4 ,Biology ,Bone morphogenetic protein 2 ,Article ,Cell Line ,Transforming Growth Factor beta1 ,Downregulation and upregulation ,Osteogenesis ,Transforming Growth Factor beta ,Bone cell ,medicine ,Adipocytes ,Humans ,Gene Silencing ,Author Correction ,Serpins ,Multidisciplinary ,Adipogenesis ,Osteoblasts ,Mesenchymal stem cell ,Osteoblast ,Cell Differentiation ,Mesenchymal Stem Cells ,Cell biology ,Clone Cells ,medicine.anatomical_structure ,Medicine ,Signal transduction ,Stem cell ,Signal Transduction - Abstract
Targeting regulatory signaling pathways that control human bone marrow stromal (skeletal or mesenchymal) stem cell (hBMSC) differentiation and lineage fate determination is gaining momentum in the regenerative medicine field. Therefore, to identify the central regulatory mechanism of osteoblast differentiation of hBMSCs, the molecular phenotypes of two clonal hBMSC lines exhibiting opposite in vivo phenotypes, namely, bone forming (hBMSC+bone) and non-bone forming (hBMSC−Bone) cells, were studied. Global transcriptome analysis revealed significant downregulation of several TGFβ responsive genes, namely, TAGLN, TMP1, ACTA2, TGFβ2, SMAD6, SMAD9, BMP2, and BMP4 in hBMSC−Bone cells and upregulation on SERPINB2 and NOG. Transcriptomic data was associated with marked reduction in SMAD2 protein phosphorylation, which thereby implies the inactivation of TGFβ and BMP signaling in those cells. Concordantly, activation of TGFβ signaling in hBMSC−Bone cells using either recombinant TGFβ1 protein or knockdown of SERPINB2 TGFβ-responsive gene partially restored their osteoblastic differentiation potential. Similarly, the activation of BMP signaling using exogenous BMP4 or via siRNA-mediated knockdown of NOG partially restored the differentiation phenotype of hBMSC−Bone cells. Concordantly, recombinant NOG impaired ex vivo osteoblastic differentiation of hBMSC+Bone cells, which was associated with SERBINB2 upregulation. Our data suggests the existence of reciprocal relationship between TGFB and BMP signaling that regulates hBMSC lineage commitment and differentiation, whilst provide a plausible strategy for generating osteoblastic committed cells from hBMSCs for clinical applications. more...
- Published
- 2019
- Full Text
- View/download PDF
5. Author Correction: Convergence of TGFβ and BMP signaling in regulating human bone marrow stromal cell differentiation
- Author
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Muthurangan Manikandan, Mona Elsafadi, Amer Mahmood, Nehad M. Alajez, Moustapha Kassem, Abdullah Aldahmash, Sami Almalki, Musaad Alfayez, and Tasneem Shinwari
- Subjects
Multidisciplinary ,Stromal cell ,Bmp signaling ,lcsh:R ,lcsh:Medicine ,Human bone ,lcsh:Q ,Convergence (relationship) ,Biology ,lcsh:Science ,Cell biology - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
- Published
- 2019
- Full Text
- View/download PDF
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