scholarly journals RNAseq of TGF-β receptor type I kinase-dependent genes in oral fibroblast exposed to milk

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Layla Panahipour ◽  
Dariush Mehdipour Moghaddam ◽  
Jila Nasirzade ◽  
Zahra Kargarpour ◽  
Reinhard Gruber
Keyword(s):  
Human Milk ◽  
Nuclear Translocation ◽  
Receptor Type ◽  
Type I ◽  
Gingival Fibroblasts ◽  
Aqueous Fraction ◽  
Tumor Necrosis Factor Ligand ◽  
Oral Tissue ◽  
Β Receptor ◽  
Smad 3

Abstract Background Milk is a rich source of natural growth factors that may support oral tissue homeostasis and wound healing. We had shown earlier that blocking TGF-β receptor type I kinase with the inhibitor SB431542 abolished the expression of IL11 and other genes in human gingival fibroblasts exposed to the aqueous fraction of milk. Our aim was to identify the entire signature of TGF-β receptor type I kinase-dependent genes regulated by the aqueous fraction of human milk. Result RNAseq revealed 99 genes being strongly regulated by milk requiring activation of the SB431542-dependent TGF-β receptor type I kinase. Among the SB431542-dependent genes is IL11 but also cadherins, claudins, collagens, potassium channels, keratins, solute carrier family proteins, transcription factors, transmembrane proteins, tumor necrosis factor ligand superfamily members, and tetraspanin family members. When focusing on our candidate gene, we could identify D609 to suppress IL11 expression, independent of phospholipase C, sphinosine-1 phosphate synthesis, and Smad-3 phosphorylation and its nuclear translocation. In contrast, genistein and blocking phosphoinositide 3-kinases by wortmannin and LY294002 increased the milk-induced IL11 expression in gingival fibroblasts. Conclusion Taken together, our data revealed TGF-β receptor type I kinase signaling to cause major changes of the genetic signature of gingival fibroblasts exposed to aqueous fraction of human milk.

scholarly journals Proteomic and genomic analysis of acid dentin lysate with focus on TGF-β signaling

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jila Nasirzade ◽  
Zahra Kargarpour ◽  
Goran Mitulović ◽  
Franz Josef Strauss ◽  
Layla Panahipour ◽  
...  
Keyword(s):  
Cellular Response ◽  
Alveolar Bone ◽  
Quantitative Polymerase Chain Reaction ◽  
Genomic Analysis ◽  
Type I ◽  
Gingival Fibroblasts ◽  
Nadph Oxidase 4 ◽  
Major Response ◽  
Collagen Membranes ◽  
Β Receptor

AbstractParticulate autologous tooth roots are increasingly used for alveolar bone augmentation; however, the proteomic profile of acid dentin lysate and the respective cellular response have not been investigated. Here we show that TGF-β1 is among the 226 proteins of acid dentin lysate (ADL) prepared from porcine teeth. RNA sequencing identified 231 strongly regulated genes when gingival fibroblasts were exposed to ADL. Out of these genes, about one third required activation of the TGF-β receptor type I kinase including interleukin 11 (IL11) and NADPH oxidase 4 (NOX4). Reverse transcription-quantitative polymerase chain reaction and immunoassay confirmed the TGF-β-dependent expression of IL11 and NOX4. The activation of canonical TGF-β signaling by ADL was further confirmed by the phosphorylation of Smad3 and translocation of Smad2/3, using Western blot and immunofluorescence staining, respectively. Finally, we showed that TGF-β activity released from dentin by acid lysis adsorbs to titanium and collagen membranes. These findings suggest that dentin particles are a rich source of TGF-β causing a major response of gingival fibroblasts.

scholarly journals Transforming Growth Factor-β Receptor Type I-dependent Fibrogenic Gene Program Is Mediated via Activation of Smad1 and ERK1/2 Pathways

2007 ◽  
Vol 282 (14) ◽  
pp. 10405-10413 ◽  
Author(s):  
Jaspreet Pannu ◽  
Sashidhar Nakerakanti ◽  
Edwin Smith ◽  
Peter ten Dijke ◽  
Maria Trojanowska
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Receptor Type ◽  
Type I ◽  
Β Receptor

scholarly journals Repression of transforming growth factor-β receptor type I promoter expression by Sp1 deficiency

Oncogene ◽  
2000 ◽  
Vol 19 (40) ◽  
pp. 4660-4667 ◽  
Author(s):  
Sumudra Periyasamy ◽  
Sudhakar Ammanamanchi ◽  
Manoranjani PM Tillekeratne ◽  
Michael G Brattain
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Receptor Type ◽  
Type I ◽  
Β Receptor

scholarly journals Human Amniotic Fluid Stem Cell-Derived Exosomes as a Novel Cell-Free Therapy for Cutaneous Regeneration

2021 ◽  
Vol 9 ◽  
Author(s):  
Yan Zhang ◽  
Jiaqing Yan ◽  
Yanhong Liu ◽  
Zhenyu Chen ◽  
Xiheng Li ◽  
...  
Keyword(s):  
Wound Healing ◽  
Amniotic Fluid ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Dermal Fibroblast ◽  
Hair Follicles ◽  
Receptor Type ◽  
Type I ◽  
Human Amniotic Fluid ◽  
Β Receptor

Adult wound healing often results in fibrotic scarring that is caused by myofibroblast aggregation. Human amniotic fluid stem cells (hAFSCs) exhibit significantly anti-fibrotic scarring properties during wound healing. However, it is little known whether hAFSCs directly or indirectly (paracrine) contribute to this process. Using the full-thickness skin-wounded rats, we investigated the therapeutic potential of hAFSC-derived exosomes (hAFSC-exo). Our results showed that hAFSC-exo accelerated the wound healing rate and improved the regeneration of hair follicles, nerves, and vessels, as well as increased proliferation of cutaneous cells and the natural distribution of collagen during wound healing. Additionally, hAFSC-exo suppressed the excessive aggregation of myofibroblasts and the extracellular matrix. We identified several miRNAs, including let-7-5p, miR-22-3p, miR-27a-3p, miR-21-5p, and miR-23a-3p, that were presented in hAFSC-exo. The functional analysis demonstrated that these hAFSC-exo-miRNAs contribute to the inhibition of the transforming growth factor-β (TGF-β) signaling pathway by targeting the TGF-β receptor type I (TGF-βR1) and TGF-β receptor type II (TGF-βR2). The reduction of TGF-βR1 and TGF-βR2 expression induced by hAFSC-exo was also confirmed in the healing tissue. Finally, using mimics of miRNAs, we found that hAFSC-exo-miRNAs were essential for myofibroblast suppression during the TGF-β1-induced human dermal fibroblast-to-myofibroblast transition in vitro. In summary, this study is the first to show that exosomal miRNAs used in hAFSC-based therapy inhibit myofibroblast differentiation. Our study suggests that hAFSC-exo may represent a strategic tool for suppressing fibrotic scarring during wound healing.

Albumin endocytosis in endothelial cells induces TGF-β receptor II signaling

2004 ◽  
Vol 286 (5) ◽  
pp. L1016-L1026 ◽  
Author(s):  
Shahid S. Siddiqui ◽  
Zeba K. Siddiqui ◽  
Asrar B. Malik
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Transforming Growth Factor ◽  
Amino Acid Sequences ◽  
Receptor Type ◽  
Structural Basis ◽  
Albumin Binding ◽  
Type I ◽  
Β Receptor ◽  
Albumin Endocytosis

Vascular endothelial cells undergo albumin endocytosis using a set of albumin binding proteins. This process is important for maintaining cellular homeostasis. We showed by several criteria that the previously described 73-kDa endothelial cell surface albumin binding protein is the 75-kDa transforming growth factor (TGF)-β receptor type II (TβRII). Albumin coimmunoprecipitated with TβRII from a membrane fraction from rat lung microvascular endothelial cells. Albumin endocytosis-negative COS-7 cells became albumin endocytosis competent when transfected with wild-type TβRII but not when transfected with a domain-negative kinase mutant of TβRII. An antibody specific for TβRII inhibited albumin endocytosis. A mink lung epithelial cell line, which expresses both the TGF-β receptor type I (TβRI) and the TβRII receptor, exhibited albumin binding to the cell surface and endocytosis. In contrast, mutant L-17 and DR-26 cells lacking TβRI or TβRII, respectively, each showed a dramatic reduction in binding and endocytosis. Albumin endocytosis induced Smad2 phosphorylation and Smad4 translocation as well as increased protein expression of the inhibitory Smad, Smad7. We identified regions of significant homology between amino acid sequences of albumin and TGF-β, suggesting a structural basis for the interaction of albumin with the TGF-β receptors and subsequent activation of TβRII signaling. The observed albumin-induced internalization of TβRII signaling may be an important mechanism in the vessel wall for controlling TGF-β responses in endothelial cells.

scholarly journals LY2109761, Transforming Growth Factor β Receptor Type I and Type II Dual Inhibitor, is a Novel Approach to Suppress Endothelial Mesenchymal Transformation in Human Corneal Endothelial Cells

2018 ◽  
Vol 50 (3) ◽  
pp. 963-972 ◽  
Author(s):  
Zhi-hua Zhang ◽  
Yu-yu Miao ◽  
Bi-lian Ke ◽  
Kun Liu ◽  
Xun Xu
Keyword(s):  
Receptor Type ◽  
Functional Markers ◽  
Type I ◽  
Type Ii ◽  
Corneal Endothelial Cells ◽  
Dual Inhibitor ◽  
In Vitro Expansion ◽  
Β Receptor ◽  
Mesenchymal Transformation

Background/Aims: Preventing undesirable endothelial-mesenchymal transformation (EnMT) with repetitious in vitro expansion of human corneal endothelial cells (CECs) is a pivotal issue in cornea regeneration. Previous studies have shown that inhibition of the TGF-β pathway reduces epithelial-mesenchymal transformation. However, its potential role in EnMT remains poorly understood. As such, the effect of LY2109761, a novel TGF-β receptor type I and type II dual inhibitor, was investigated on EnMT. Methods: CECs cultured with various concentrations of LY2109761 were evaluated for their growth rate and phenotype. Additionally, the expression of functional markers (sodium-potassium pump Na+/K+-ATPase and the tight junction protein ZO-1) and mesenchymal markers (CD73, fibronectin, and vimentin) was detected using immunostaining and western blot. The mRNA expressions were also assayed by real-time polymerase chain reaction analysis. Results: At a 1 μM concentration, LY2109761 did not influence the proliferation of CECs and subsequent experiments were therefore performed using this concentration. Furthermore, CECs cultured in the presence of 1 μM LY2109761 maintained their ability to grow as a monolayer of hexagonal-shaped cells. The expression of functional markers increased in LY2109761-treated CECs, while the expression of mesenchymal markers decreased (both in protein and mRNA levels). Conclusion: Inhibition of TGF-β receptor type I and type II by LY2109761 maintained the phenotype of CECs and inhibited the EnMT process. These results indicate the possible continuous in vitro expansion of CECs with normal function.

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