| 2014 |
Thy1 (CD90) blocks adipogenesis by inhibiting the activity of the Src family kinase Fyn, which in turn decreases PPARγ transcriptional activity by more than 60%. Thy1-null mice gained 30% more weight than controls on a high-fat diet, and overexpression of Thy1 in 3T3-L1 cells blocked adipocyte formation and reduced FABP4 expression 5-fold. |
Thy1 overexpression/knockout in mouse model, PPARγ reporter assays, genetic and pharmacologic Fyn inhibition (siRNA + PP2 inhibitor), Western blotting |
FASEB journal |
High |
25416548
|
| 2008 |
Thy-1 activation in lung myofibroblasts up-regulates FasL expression via Src family kinases, specifically Fyn. Thy-1 activation first causes translocation of FasL to the membrane surface, then induces de novo synthesis of FasL at mRNA and protein levels. Src family kinase inhibitor PP2 and Fyn-specific siRNA both blocked this induction. |
Anti-Thy1 antibody activation, SFK inhibitor PP2, Fyn-specific siRNA knockdown, flow cytometry, RT-PCR, Western blot |
American journal of respiratory cell and molecular biology |
High |
18676775
|
| 2006 |
Thy-1 expression predetermines fibroblast lineage commitment: only Thy-1(+) human myometrial and orbital fibroblasts differentiated into myofibroblasts (assessed by α-SMA expression) in response to TGF-β or platelet concentrate, whereas only Thy-1(−) fibroblasts differentiated into lipofibroblasts after treatment with PPARγ agonists. |
FACS-sorted fibroblast subsets, TGF-β treatment, PPARγ agonist treatment, α-SMA immunostaining, lipid droplet accumulation assay |
The American journal of pathology |
Medium |
14507638
|
| 2006 |
Thy-1(−) lung fibroblasts show significantly greater myofibroblast differentiation, collagen matrix contraction, and resistance to apoptosis compared with Thy-1(+) cells. Transfection of Thy-1 into Thy-1(−) cells inhibited collagen matrix contraction and reduced cell survival, directly demonstrating that Thy-1 regulates myogenic gene expression and myofibroblastic differentiation. |
FACS-sorted rat lung fibroblasts, TGF-β/ET-1/CTGF stimulation, floating collagen matrix contraction assays, apoptosis assays, Thy-1 transfection into Thy-1(−) cells, RT-PCR, immunoblotting |
American journal of respiratory cell and molecular biology |
High |
16960126
|
| 2008 |
Thy-1 promoter CpG islands are hypermethylated in Thy-1(−) lung fibroblasts and in fibroblastic foci of IPF tissue, silencing Thy-1 expression. Treatment with DNA methyltransferase inhibitors restores Thy-1 expression in Thy-1(−) fibroblasts, establishing promoter hypermethylation as a mechanism of Thy-1 silencing in pulmonary fibrosis. |
RT-PCR, methylation-specific PCR, bisulfite genomic sequencing, MSP-in situ hybridization on fibrotic tissue, DNMT inhibitor treatment |
American journal of respiratory cell and molecular biology |
High |
18556592
|
| 2010 |
Histone deacetylase inhibitor trichostatin A (TSA) restores Thy-1 expression in Thy-1(−) lung fibroblasts by enriching histone H3K4 trimethylation and H4 acetylation at the Thy-1 locus, while depleting repressive H3K27 trimethylation. TSA treatment also caused demethylation of previously hypermethylated CpG sites in the Thy-1 promoter, indicating that histone modifications regulate DNA methylation at this locus. |
TSA treatment, chromatin immunoprecipitation (ChIP) for histone marks, bisulfite sequencing, RT-PCR, global DNA methylation assays |
American journal of respiratory cell and molecular biology |
High |
20724553
|
| 2015 |
TGF-β1 epigenetically suppresses Thy-1 expression in primary lung fibroblasts by activating DNMT1 and inducing Thy-1 promoter methylation. siRNA knockdown of DNMT1 attenuated TGF-β1-induced DNMT activity and rescued Thy-1 expression, also inhibiting downstream α-SMA and collagen Col1A1 expression. |
TGF-β1 treatment, 5-AZA co-treatment, DNMT1 siRNA knockdown, quantitative methyl PCR, RT-PCR, Western blot, immunofluorescence |
American journal of physiology. Cell physiology |
High |
26333597
|
| 2009 |
Loss of Thy-1 in Thy-1(−/−) mice leads to impaired alveolarization, increased TGF-β signaling, altered cell proliferation, and increased collagen/elastin deposition. Administration of TGF-β neutralizing antibody (1D11) to Thy-1(−/−) mice improved alveolar development, establishing that Thy-1-expressing fibroblasts inhibit TGF-β activation and thereby support normal alveolar development. |
Thy-1 null mouse model, hypoxia exposure, lung histology, lung function measurement, TGF-β neutralizing antibody treatment, immunostaining |
American journal of physiology. Lung cellular and molecular physiology |
High |
19270178
|
| 2019 |
Soluble Thy-1-Fc (sThy-1) reversed TGF-β1-induced myofibroblast differentiation in vitro in a dose-dependent manner via its integrin-binding RGD motif (RLE-mutated Thy-1 was inactive), and resolved established lung fibrosis in vivo after bleomycin or doxycycline-induced TGF-β1 overexpression. Thy1-null mice showed progressive αv integrin activation and myofibroblast accumulation, identifying an αv integrin-driven feedback loop sustained by loss of Thy-1. |
Thy1-null mouse model, bleomycin/doxycycline fibrosis models, soluble Thy-1-Fc treatment in vivo, RLE-mutant Thy-1 control, in vitro myofibroblast differentiation assays, αv integrin activation assessment |
JCI insight |
High |
31672942
|
| 2010 |
Thy1 (CD90) is expressed by lymphatic endothelial cells (but not blood vascular endothelial cells) and mediates adhesion of tumor cells and leukocytes to lymphatic endothelium. Blockade of Thy1 inhibited tumor cell adhesion to lymphatic endothelial cells in vitro, and Thy1-deficient mice showed markedly reduced experimental lung and lymph node metastasis of B16/F10 melanoma cells. |
Comparative transcriptional profiling, FACS, immunofluorescence, anti-Thy1 blockade in adhesion assays, Thy1(−/−) mouse experimental metastasis model |
Experimental cell research |
High |
20599951
|
| 2012 |
Thy-1 on endothelial cells mediates adhesion of melanoma cells via αvβ3-integrin on tumor cells. Thy-1-deficient mice showed reduced experimental lung and lymph node metastasis without affecting primary tumor growth, T-cell activation, or angiogenesis, establishing Thy-1–integrin adhesion as a specific pro-metastatic mechanism. |
Thy-1(−/−) mouse experimental and spontaneous metastasis models, in vitro adhesion assays, VEGF/TNF-α induction of Thy-1 on EC |
The American journal of pathology |
High |
23159525
|
| 2006 |
Thy-1 on activated human dermal microvascular endothelial cells mediates neutrophil adhesion specifically via interaction with the β2-integrin Mac-1. Blocking Thy-1 on endothelial cells or Mac-1 on neutrophils significantly inhibited adhesion; psoriatic neutrophils showed increased adhesion to Thy-1 transfectants compared with healthy controls. |
Thy-1 transfected cell adhesion assay, blocking antibodies against Thy-1 and Mac-1, HDMEC adhesion assays, flow cytometry |
The Journal of investigative dermatology |
Medium |
16374458
|
| 2005 |
The αX I-domain of the β2-integrin αXβ2 (CD11c/CD18) binds Thy-1 in a specific, divalent cation-dependent manner with a Kd of 1.16 μM. Amino acid substitutions in the βD-α5 loop of the αX I-domain (D249, KE243/244) reduced binding affinity, identifying the βD-α5 loop/α5 helix region as the Thy-1 recognition site. |
Recombinant I-domain binding assay, site-directed mutagenesis of αX I-domain, kinetic/affinity measurements |
Biochemical and biophysical research communications |
Medium |
15850796
|
| 2015 |
THY-1 mediates HCMV entry at the initial infection step (within the first 60 minutes). Anti-THY-1 antibody and siRNA knockdown impaired infectivity, blocked HCMV-induced PI3-K/Akt activation required for entry, and soluble THY-1 protein blocked infection during but not after virus internalization. THY-1 was shown to interact with HCMV glycoproteins gB and gH by co-immunoprecipitation. |
THY-1 siRNA knockdown, anti-THY-1 antibody blocking, exogenous THY-1 expression, soluble THY-1 protein competition, co-immunoprecipitation with gB and gH, PI3-K/Akt pathway activation assay |
PLoS pathogens |
High |
26147640
|
| 2018 |
Thy-1 deficiency in mice leads to decreased bone volume, bone formation rate, and elevated cortical porosity, accompanied by reduced osteogenic Wnt ligands and increased Wnt inhibitors (sclerostin, dickkopf-1), and increased body fat mass. MSCs from Thy-1(−/−) mice showed decreased osteoblast differentiation and increased adipogenic differentiation, establishing Thy-1 as a regulator of MSC fate between osteogenic and adipogenic lineages. |
Thy-1(−/−) mouse model, micro-CT bone analysis, histomorphometry, MSC differentiation assays, Wnt pathway gene expression analysis, serum Thy-1 measurement in patients |
Science translational medicine |
High |
30089635
|
| 2018 |
Thy1 is a positive regulator of osteoblast differentiation. Thy1 KO mice fed a high-fat diet showed significantly reduced trabecular bone volume. In vitro, osteogenic conditions increased Thy1 expression during osteoblast differentiation, and absence of Thy1 attenuated osteoblastogenesis. |
Thy1 KO mouse model, micro-CT, histomorphometry, in vitro osteogenic differentiation assays |
FASEB journal |
Medium |
29401595
|
| 2022 |
THY1 inhibits epidermal YAP activity through two converging mechanisms: (1) by suppressing integrin-β1-SRC signaling that promotes cell-matrix adhesion, and (2) by maintaining an adherens junction complex that retains YAP in the cytoplasm. THY1 deficiency causes YAP nuclear translocation and increased proliferation even at high cell density. Thy1(−/−) mice display enhanced wound repair and hair follicle regeneration due to increased YAP-dependent proliferation. |
Thy1(−/−) mouse model, wound healing and hair follicle assays, integrin-β1-SRC pathway analysis, adherens junction complex dissociation assays, YAP localization imaging, proliferation assays |
Nature cell biology |
High |
35798842
|
| 2021 |
Thy-1-αVβ3 integrin interaction in cancer cells (MDA-MB-231 breast cancer and B16F10 melanoma) triggers a Ca2+/hemichannel/ATP/P2X7 receptor signaling axis that promotes cell migration and invasion. β3 integrin silencing in cancer cells reduced transvasation through an endothelial monolayer and prevented lung metastasis in a preclinical mouse model. |
Thy-1 stimulation assay, intracellular Ca2+ measurement, connexin/pannexin inhibitors, P2X7 receptor pharmacologic blockade, β3 integrin siRNA, endothelial transmigration assay, in vivo mouse metastasis model |
Frontiers in cell and developmental biology |
High |
33511115
|
| 2017 |
CD90 expression in glioblastoma cells promotes adhesion and migration through enhanced SRC and FAK signaling. Modulation of CD90 expression in GBM cells dramatically affected their adhesion and migration in vitro, and CD90 expression induced invasive phenotypes in orthotopic xenografts in vivo. Pharmacologic inhibition of SRC/FAK blunted adhesion/migration in CD90-positive cells. |
CD90 siRNA knockdown in GBM cells, CD90 complementation in CD90-negative U87 cells, orthotopic xenograft models, SRC/FAK inhibitor treatment, GBM patient transcriptome analysis |
Clinical cancer research |
Medium |
28939749
|
| 2015 |
CD90 promotes liver cancer stem cell properties via a signal axis involving its RLD integrin-binding domain, β3 integrin, and AMPK/mTOR pathway, leading to upregulation of CD133. Mutation of the integrin-binding RLD domain of CD90 and silencing of β3 integrin both attenuated CD133 induction and anchorage-independent growth. Ectopic CD90 expression induced mTOR phosphorylation and AMPK dephosphorylation. |
CD90 ectopic expression and shRNA knockdown, RLD-domain mutant CD90, β3 integrin shRNA, mTOR/AMPK phosphorylation Western blot, anchorage-independent growth assay, xenograft tumorigenicity assay |
Oncotarget |
Medium |
26556861
|
| 2016 |
CD90 inhibits ovarian cancer anchorage-independent growth and tumor formation in vivo via β3 integrin-dependent suppression of CD133 and the AMPK/mTOR axis. Mutation of CD90's RLE (integrin-binding) domain to RLD abolished tumor-suppressive effects, and β3 integrin shRNA restored anchorage-independent growth and CD133 expression in CD90-overexpressing cells. |
CD90 overexpression in SKOV3 cells, RLE-to-RLD domain mutation, β3 integrin shRNA, anchorage-independent growth assay, xenograft tumor formation, ALDH activity, Western blot for mTOR/AMPK |
International journal of oncology |
Medium |
27633757
|
| 2016 |
Reduction of CD90 expression in mesenchymal stromal cells using shRNA lentiviral vectors enhanced osteogenic and adipogenic differentiation in vitro and caused a decrease in CD44 and CD166 expression, demonstrating that CD90 controls MSC differentiation commitment. |
CD90-targeted shRNA lentiviral knockdown, osteogenic/adipogenic differentiation assays, flow cytometry for surface markers |
Stem cell research & therapy |
Medium |
27465541
|
| 2017 |
Environmental chemical TBBPA reduces Thy1 expression in human and mouse (pre)adipocyte cells by inducing miR-103 (and miR-107), which directly targets the Thy1 mRNA 3'UTR. Reduced Thy1 levels promoted adipogenesis; miR-103 induction by TBBPA was confirmed and luciferase reporter assays validated miR-103 targeting of Thy1 mRNA. |
Flow cytometry, Western blotting, qPCR for Thy1 expression, miRNA qPCR, luciferase reporter assay with Thy1 3'UTR, miR-103/107 prediction and validation |
Toxicological sciences |
Medium |
28329833
|
| 2007 |
FcεRI-enriched membrane domains and Thy-1-enriched membrane domains have distinct lipid compositions: FcεRI domains contain approximately 2-fold more sphingomyelin and higher cholesterol-to-fatty acid ratios than Thy-1 microdomains, and plasmenyl-glycerophosphoethanolamine (plasmalogen GPE) is 2.5–3 times more abundant in FcεRI domains. Thy-1 domains are devoid of FcεRI subunits. |
Magnetic bead isolation of receptor/Thy-1 enriched membrane vesicles (detergent-free), lipidomics by positive and negative ion electrospray mass spectrometry, protein analyses |
Journal of lipid research |
Medium |
17387221
|
| 2012 |
Thy-1 siRNA knockdown in skin wound regions retarded wound repair in mice, reduced re-epithelialization quality, and caused continuously increased TGF-β1 levels at wound sites. In fibroblasts, Thy-1 affects cell migration into wounds, cell proliferation, and cytoskeletal structure. |
Thy-1 siRNA injection at wound sites in mice, wound healing rate measurement, TGF-β1 measurement, fibroblast scratch assay, proliferation and cytoskeletal imaging |
Journal of dermatological science |
Medium |
23312577
|
| 2019 |
CD90+ fibroblasts in the colon crypt express class 3 semaphorins (Sema3) that are required for their supportive effect on intestinal organoid growth, in addition to expressing stem cell niche factors Grem1, Wnt2b, and R-spondin3. |
Stromal cell phenotyping, organoid co-culture assays, gene expression analysis (Sema3, Grem1, Wnt2b, R-spondin3), functional blockade experiments |
Cell reports |
Medium |
30917322
|
| 2022 |
USF1 transcription factor directly regulates CD90 expression in glioblastoma stem cells (confirmed by luciferase assay and ChIP-qPCR). CD90 of GSCs functions as a physical anchor for monocyte/macrophage adhesion, supporting immunosuppressive TAM features that in turn enhance GSC stemness. CD90 overexpression rescued stemness properties in USF1-knockdown GSCs. |
USF1 siRNA knockdown, luciferase reporter assay, ChIP-qPCR for USF1 binding to CD90 promoter, CD90 overexpression rescue, co-culture of GSCs with macrophages, in vivo GBM models |
Neuro-oncology |
Medium |
35287174
|
| 2018 |
Breast cancer cells undergoing epithelial-mesenchymal transition enhance neutrophil TIMP-1 secretion via CD90 in a cell-contact manner. In vivo, CD90 blockade significantly reduced metastasis in tumor-bearing mice, supporting CD90 as a juxtacrine signal in the CD90-TIMP-1 pro-metastatic loop. |
Transwell and 3D Matrigel co-culture of neutrophils and cancer cells, antibody microarray cytokine screening, CD90 blockade in vivo, TIMP-1 neutralization in vivo |
Clinical cancer research |
Medium |
30482778
|
| 2004 |
Thy-1 expression in neuronal cells is regulated by iron availability: iron chelation significantly decreased Thy-1 expression in PC12 cells in a dose- and time-dependent manner. Brain homogenates from iron-deficient rats showed decreased Thy-1 levels, and Thy-1 concentration in the substantia nigra of Restless Legs Syndrome patients (with lower iron) was less than half that of controls. |
Iron chelation in PC12 cells, Western blot for Thy-1 and transferrin receptor, rat iron-deficiency model, brain tissue homogenate analysis from RLS patients |
Journal of the neurological sciences |
Medium |
15140607
|
| 2022 |
CD90 is a downstream transcriptional effector of the NOTCH1 pathway in intrahepatic cholangiocarcinoma: NOTCH1 silencing by siRNA decreased HES1 and THY1 expression, and the NOTCH transcriptional regulator RBPJ was shown to bind putative sites on the THY1 promoter by ChIP assay. |
NOTCH1 siRNA knockdown, RT-PCR for HES1 and THY1, ChIP for RBPJ binding to THY1 promoter, CD90 OE/KD xenograft models, γ-secretase inhibitor (Crenigacestat) treatment |
Journal of experimental & clinical cancer research |
Medium |
35172861
|