| 2010 |
THSD7A is expressed at the leading edge of migrating HUVECs and co-localizes with αVβ3 integrin and paxillin; overexpression of a THSD7A C-terminal fragment inhibited HUVEC migration and tube formation, while suppression enhanced migration and tube formation, and the distribution was dispersed from focal adhesions after actin cytoskeleton disruption, implicating THSD7A in cytoskeletal organization. |
HUVEC overexpression/knockdown with migration and tube formation assays, immunolocalization with αVβ3 integrin and paxillin, actin disruption experiments |
Journal of cellular physiology |
Medium |
20020485
|
| 2011 |
Full-length THSD7A is membrane-associated and N-glycosylated; a soluble form is released into culture medium. Soluble THSD7A promotes HUVEC migration, tube formation, filopodia formation, and vessel branching in zebrafish SIV assays. It increases FAK phosphorylation and alters vinculin distribution, indicating regulation of cytoskeletal reorganization via a FAK-dependent mechanism. |
HEK293T overexpression, glycosylation assays, HUVEC migration/tube formation/sprouting assays, zebrafish SIV assay, FAK phosphorylation immunoblot, vinculin localization |
PloS one |
Medium |
22194972
|
| 2011 |
Zebrafish Thsd7a is expressed along the ventral neural tube at sites correlating with angiogenic intersegmental vessel (ISV) growth paths; morpholino knockdown of Thsd7a causes lateral deviation of angiogenic endothelial cells and aberrant ISV patterning, establishing Thsd7a as a neural guidance molecule required for directed EC migration during embryonic angiogenesis. |
Morpholino knockdown in zebrafish, in situ hybridization, ISV patterning analysis |
Developmental dynamics |
Medium |
21520329
|
| 2016 |
Zebrafish thsd7a is expressed specifically in primary motor neurons; knockdown disrupts primary motor neuron formation and ISV sprouting. Thsd7a morphants phenocopy loss of Notch-dll4 signaling, and transcript profiling showed downregulation of notch1b and its downstream targets vegfr2/3 and nrarpb, placing Thsd7a upstream of Notch-dll4 signaling in angiogenic sprouting. |
Morpholino knockdown in Tg(kdr:EGFP/mnx1:TagRFP) double transgenic zebrafish, transcript profiling, phenotypic comparison with Notch-dll4 loss |
Journal of biomedical science |
Medium |
27484901
|
| 2018 |
THSD7A knockdown in endothelial cells attenuates monocyte adhesion by decreasing expression of ICAM, L-selectin, and ITGB2, demonstrating a functional role for THSD7A in regulating monocyte-endothelial adhesion molecules. |
siRNA knockdown in endothelial cells, monocyte adhesion assay, ICAM/L-selectin/ITGB2 expression analysis |
Arteriosclerosis, thrombosis, and vascular biology |
Medium |
29472232
|
| 2019 |
The immunodominant B-cell epitope of THSD7A for autoantibodies in membranous nephropathy is located in a 28-mer sequence (T28mer) in the N-terminal domain, with sequence homology to the major PLA2R epitope. Kallikrein protease cleavage within this sequence abolishes antibody reactivity. Cross-reactivity of PLA2R and THSD7A autoantibodies was detected at the peptide but not the protein level. |
Western blot and slot blot with THSD7A protein fragments and peptides, bio-layer interferometry for real-time interaction, kallikrein protease cleavage, homology modelling, B-cell epitope prediction |
Journal of autoimmunity |
Medium |
31395435
|
| 2022 |
Immune complexes formed by predominantly IgG4 anti-THSD7A autoantibodies activate complement exclusively via the alternative pathway; C3b fixation is abolished in factor B-depleted sera, partially inhibited in C4-depleted sera, unchanged in C1q-depleted sera, and occurs in Mg-EGTA buffer, demonstrating that the classical and lectin pathways are dispensable while the alternative pathway is necessary and sufficient. |
In vitro complement fixation assays with factor B-, C4-, C1q-depleted sera and Mg-EGTA buffer; IgG subclass analysis of patient sera |
Frontiers in immunology |
Medium |
35874690
|
| 2024 |
Anti-THSD7A antibodies in a mouse MN model cause loss of slit diaphragm proteins (nephrin, NEPH1) at the protein level without transcriptional downregulation, induce transcriptomic/proteomic reconfiguration involving disrupted podocyte adhesion, cytoskeletal dynamics, upregulation of ubiquitin-proteasome components, cathepsins, and ADAM proteases. In C3-deficient mice, these proteolytic and SD protein changes persist, indicating complement-independent pathomechanisms. Podocyte-specific Thsd7a-KO mice are completely protected from MN development upon antibody transfer. Interactome analysis identified THSD7A in a complex with integrin α3, linking THSD7A to pathogenic regulation of cytoskeleton, adhesion, and membrane signaling. |
Podocyte-specific Thsd7a-KO mice, anti-THSD7A antibody transfer MN model, transcriptome and proteome analyses, C3-deficient mice, interactome analysis (Co-IP/MS implied), in vitro primary podocyte exposure to antibody |
JCI insight |
High |
41746732
|
| 2024 |
THSD7A is carried in exosomes (small extracellular vesicles) from both cancer cells and neurons; add-back of purified THSD7A to endoglin-knockdown cancer cells or exosome-inhibited neurons rescues filopodia defects. THSD7A induces filopodia formation through activation of the Rho GTPase Cdc42. |
Exosome inhibition and rescue experiments, proteomic analysis of cancer cell-derived SEVs, add-back of purified THSD7A protein, Cdc42 activity assays, filopodia quantification in cancer cells and neurons |
bioRxivpreprint |
Medium |
|
| 2016 |
VEGF-A upregulates THSD7A expression in cultured endothelial cells, particularly under T-helper type 2-prone conditions, suggesting VEGF-A as a transcriptional regulator of THSD7A outside the kidney relevant to MN pathogenesis. |
In vitro VEGF-A stimulation of cultured endothelial cells with measurement of THSD7A expression; immunohistochemistry of ALHE tumor tissue |
American journal of kidney diseases |
Low |
30554801
|
| 2022 |
Inhibition of super-enhancers reduces THSD7A expression in podocytes, and ERK inhibition enhances THSD7A expression, indicating that THSD7A transcription is regulated by super-enhancer activity and ERK signaling in podocytes. |
Super-enhancer inhibitor treatment and ERK inhibitor treatment in cultured podocytes with THSD7A expression quantification |
Cell biochemistry and function |
Low |
35670653
|
| 2024 |
In a mouse model of THSD7A-associated MN, complement depletion with cobra venom factor only partially attenuated proteinuria and glomerular injury; anti-THSD7A antibody exposure in primary podocytes caused actin cytoskeleton disruption, podocyte hypermobility, oxidative stress, and apoptosis even after complement inactivation, establishing complement-independent autonomous podocyte injury as a pathomechanism. |
Mouse MN model with cobra venom factor complement depletion, in vitro primary podocyte exposure to anti-THSD7A antibody with complement inactivation, actin cytoskeleton imaging, oxidative stress and apoptosis assays |
Frontiers in pharmacology |
Medium |
39086386
|