Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma characterized by a myxoid matrix and a distinctive lobulated architecture, composed of cords and clusters of uniform round-to-rhabdoid cells. At the...Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma characterized by a myxoid matrix and a distinctive lobulated architecture, composed of cords and clusters of uniform round-to-rhabdoid cells. At the molecular level, EMC is defined by specific gene fusions involving NR4A3, most frequently EWSR1::NR4A3. The responses to conventional chemotherapy are limited, and the prognosis for patients with advanced or metastatic disease remains poor. We successfully developed the NCC-EMC1-C1 cell line using surgically resected tumor tissue from a patient with EMC. NCC-EMC1-C1 cells exhibited constant proliferation in monolayer culture, spheroid formation in low-attachment plates, and migration. High-throughput screening of 221 anticancer drugs using NCC-EMC1-C1 identified three candidates, brigatinib, panobinostat, and romidepsin, that demonstrated low IC values. These data indicated the utility of NCC-EMC1-C1 for the experiments based on screening. We conclude that NCC-EMC1-C1 is a valuable tool for preclinical and basic research on EMC.
Beckwith-Wiedemann syndrome (BWS) is a human genomic imprinting disorder mainly caused by an imprinting abnormality in the chromosome 11p15.5 region. It is rare and sporadic with unclear etiology and pathogenesis. We ide...Beckwith-Wiedemann syndrome (BWS) is a human genomic imprinting disorder mainly caused by an imprinting abnormality in the chromosome 11p15.5 region. It is rare and sporadic with unclear etiology and pathogenesis. We identified a family with a clustering of BWS cases arising from methylation abnormality of IC1 region. An induced pluripotent stem-cell line (BWS iPSC) was generated from peripheral blood mononuclear cells (PBMCs) of one affected family member using a non-integrating reprogramming method. This cell line could be further differentiated into multiple lineages, enabling us to determine the relationship of the expression of abnormal imprinting genes in BWS to cellular phenotypes, thus elucidating the pathogenic mechanisms of BWS. In future, the multi-lineage cells can be used to test various innovative therapies, providing conceptual validation for the treatment of BWS.
Prostate cancer is the second leading cause of cancer-related deaths in males that has an unfavorable outcome. Autophagy-related genes (ARGs) contribute to the process of tumorigenesis and metastasis of prostate cancer....Prostate cancer is the second leading cause of cancer-related deaths in males that has an unfavorable outcome. Autophagy-related genes (ARGs) contribute to the process of tumorigenesis and metastasis of prostate cancer. This study aimed to identify ARGs that could serve as reliable and non-invasive biomarkers for evaluating prostate cancer prognosis. The expression profiles of ARGs were identified in prostate cancer specimens with good prognosis (n = 98) and poor prognosis (n = 42). A series of in vitro assays were performed to explore the function and mechanisms of ARGs in malignant progression of prostate cancer. Receiver operating characteristic curve were utilized to evaluate the predictive potential of ARGs for prostate cancer prognosis. Patients with poor prognosis exhibited higher expression of baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) and lower expression of neuregulin 2 (NRG2) compared to those with good prognosis. BIRC5 served as independent risk factors for prostate cancer prognosis, and enhanced BIRC5 expression promoted cells viability, migration, and invasion, but the autophagy activator rapamycin could counteract the effects of the BIRC5 gene. Conversely, NRG2 acted as a protective factor for prostate cancer prognosis, and elevated NRG2 expression suppressed cells viability, migration, and invasion, but the autophagy inhibitor 3-Methyladenine could reverse the effects of the NRG2 gene. The combination of BIRC5, NRG2 with prostate specific antigen (PSA) demonstrated significant predictive value for prostate cancer prognosis. BIRC5 and NRG2 genes participate in the progression of prostate cancer by regulating autophagy. BIRC5 and NRG2 have the potential to serve as valuable biomarkers for the prognosis of prostate cancer.
High-risk HPV subtypes impact the immune response in cervical cancer. Tumor-associated macrophages (TAMs) are well known to contribute to tumor development by regulating the immune response. This study aimed to analyze t...High-risk HPV subtypes impact the immune response in cervical cancer. Tumor-associated macrophages (TAMs) are well known to contribute to tumor development by regulating the immune response. This study aimed to analyze the mechanism of TAMs by the enhancer of zeste homolog 2 (EZH2) in HPV16 cervical cancer. The HPV16 cervical cancer cells, SiHa and CaSki, were treated with increasing concentrations of EZH2 inhibitor EPZ6438 (5, 10, 20, 40, 80 μM) for 24 h. The KDM6A expression is suppressed in a concentration-dependent manner when EZH2 activity is inhibited. Then, the cancer cells were transfected with pcDNA-control or pcDNA-KDM6A, and treated with the IC of EPZ6438. The cell viability, levels of IL-6 and CXCL1, and p-Akt(s473)/Akt proteins were measured. The PMA-treated THP-1 cells were induced into M2 macrophages by IL-4 and IL-13. The M2 macrophages were cocultured with the conditioned cancer cells to observe the M2 polarization. In vivo experiments, the effects of EZH2 inhibition on tumor growth were investigated in nude mice. EZH2 inhibition suppressed the cell viability and inflammatory response by suppressing KDM6A in HPV16 cervical cancer cells. KDM6A overexpression suppressed the effects of EZH2 inhibition on cell viability and inflammatory response. EZH2 inhibition in cancer cells suppressed the M2 macrophages, and its mechanism was related to the KDM6A-mediated inflammatory response. In nude mice models, EZH2 inhibition effectively reduced tumor growth by regulating KDM6A. EZH2 regulated the KDM6A-mediated inflammatory response, thus affecting the polarization of M2 macrophages, leading to tumor growth in HPV16 cervical cancer. This study provided an insight into the immune modulation of EZH2 in HPV16 cervical cancer.
Skeletal progenitor-enriched cells, also referred to as skeletal stem cell (SSC)-like cells, are multipotent progenitors that underpin advancements in bone bioengineering and regenerative therapy. Platelet-rich plasma-de...Skeletal progenitor-enriched cells, also referred to as skeletal stem cell (SSC)-like cells, are multipotent progenitors that underpin advancements in bone bioengineering and regenerative therapy. Platelet-rich plasma-derived exosomes (PRP-EXOs) exhibit promising capabilities for enhancing osteogenic repair and addressing bone-defect challenges. Nonetheless, whether PRP-EXOs promote bone regeneration and repair by affecting SSC-like cells remains unclear. This study aimed to investigate the effects of PRP-EXOs on SSC-like cells and bone-defect regeneration and repair. PRP-EXOs were purified from rat-derived PRP, and SSC-like cells were obtained via collagenase digestion of femoral and tibial bone tissues. PRP-EXOs were identified by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. The effects of PRP-EXOs on cell viability, proliferation, migration, and osteogenic differentiation were also assessed. Femoral bone-defect models were constructed in rats and evaluated for bone regeneration and repair using microcomputed tomography, bone parameter analysis, and histological assessment. We successfully extracted PRP-EXOs and isolated SSC-like cells from Sprague Dawley rats. Incubation with PRP-EXOs increased cell viability, promoted cell proliferation and migration, and strengthened the osteogenic differentiation of SSC-like cells. Furthermore, PRP-EXO treatment reduced weight loss and accelerated new bone formation and repair in rats with femoral bone defects, accompanied by improvements in bone mineralization and collagen formation. The promotion of bone-defect repair by PRP-EXOs may depend on their promoting effects on the proliferation, migration, and osteogenic differentiation of SSC-like cells, suggesting that PRP-EXOs may be important in bone-defect treatment.
Dedifferentiated chondrosarcoma (DDCS) is a rare and aggressive subtype of chondrosarcoma, characterized by the coexistence of a high-grade spindle or pleomorphic tumor that lacks a substantial cartilaginous matrix. Nota...Dedifferentiated chondrosarcoma (DDCS) is a rare and aggressive subtype of chondrosarcoma, characterized by the coexistence of a high-grade spindle or pleomorphic tumor that lacks a substantial cartilaginous matrix. Notably, it shows a mutant IDH1 incidence of over 80%. This study established a novel DDCS cell line with an IDH1 mutation, TK-DDCS1, derived from the right ilium of a 67-year-old Japanese female patient. TK-DDCS1 cells maintain the undifferentiated DDCS phenotype with the IDH1p.R132L mutation. The IDH1R132 mutation is known to be associated with a poor prognosis for chondrosarcoma, and the p.R132L mutation is a novel variant among the registered DDCS cell lines in the Cellosaurus database. The mutant IDH1 inhibitor, DS-1001b, inhibited the proliferation of TK-DDCS1 in a dose-dependent manner in both two-dimensional and spheroid cultures. The tumorigenicity of TK-DDCS1 was demonstrated through xenografting into EGFP-transgenic BALB/c Rag2-/-/Jak3-/- (EGFP-BRJ) mice, where the tumors exhibited undifferentiated phenotypes of DDCS in both morphological and immunohistochemical features. Thus, TK-DDCS1 serves as a valuable model for investigating the characteristics of DDCS and exploring molecular targeted therapies.
The pathogenesis of uterine carcinosarcoma (UCS) remains unclear due to a few mature cell lines. Herein, we established a new cell line, ESCA, from a Chinese woman. Especially, three sublines, named ESCA-2, ESCA-3, ESCA-...The pathogenesis of uterine carcinosarcoma (UCS) remains unclear due to a few mature cell lines. Herein, we established a new cell line, ESCA, from a Chinese woman. Especially, three sublines, named ESCA-2, ESCA-3, ESCA-5, were isolated based on the rate of cells' different sedimentation. All ESCA cells have been subcultured for more than 60 generations. ESCA sublines display different cell morphology and growth characteristics, as well as have different sensitivity to chemotherapeutic drugs. ESCA was most sensitive to paclitaxel and carboplatin, while ESCA-2 was most sensitive to ifosfamide. Besides, ESCA showed severe chromosome karyotype abnormalities and abnormal number of chromosomes. Whole exome sequence showed ESCA and its sublines, as well as tissue block shared similar single nucleotide variants, such as TP53, TRRAP mutations, while relatively large differences in mutational signature abundance. When all ESCA cells were xenotransplanted subcutaneously into BALB/c-nu mice, they developed into tumors that resembled the original tumor with positive AE1/3 and Vimentin in immunohistochemical staining. Interestingly, the transplanted tumor from ESCA-5 proliferated fastest with a relatively low level of glucose uptake evaluated by micro-PET/CT scanning. Taken together, ESCA and its sublines may be valuable tools to explore the molecular mechanism of UCS.
Hypoxia is a critical mechanism within the microenvironment of tumors. Exosomes, serve as conduits for intercellular communication and transport the biomolecule miRNA by facilitating intercellular signal exchange, which...Hypoxia is a critical mechanism within the microenvironment of tumors. Exosomes, serve as conduits for intercellular communication and transport the biomolecule miRNA by facilitating intercellular signal exchange, which partially regulate cancer metastasis. Our research investigated whether the role of hypoxic breast cancer cell-derived exosomal miR-143-3p in cancer progression. Real-time PCR explored miR-143-3p expression in hypoxia breast cancer cell-derived exosomes. Co-culturing of breast cancer with hypoxia exosome-primed M0 macrophages, transwell detected the invasiveness of breast cancer cells. Western blot showed the effect of hypoxia exosomes on the levels of M2 makers in macrophages and the epithelial-mesenchymal transition (EMT) indicators in breast cancer cells. Bioinformatics prediction and dual luciferase reporter assay determined the interaction between miR-143-3p and RICTOR. We found that exosomal miR-143-3p expression was downregulated in hypoxic conditions. Hypoxia breast cancer cell-derived exosomal miR-143-3p negatively correlated with the presentation of the M2 macrophage marker CD206 and regulated the levels of Arg-1, CD206 and CD163 mRNA levels. In addition, hypoxia exosome-mediated polarization of M2 macrophages promotes breast cancer cell migration and invasion. Mechanistically, miR-143-3p acted antagonistically with RICTOR, thereby suppressing macrophage M2 polarization. In summary, our study reveals that the hypoxia downregulates the exosomal miR-143-3p derived from breast cancer cells to increase macrophage RICTOR expression, thereby promoting M2 macrophage polarization to enhance breast cancer cell invasiveness, suggesting that miR-143-3p may be a candidate molecule for microRNA alternative therapy in breast cancer.
Digestive system tumors are the most common tumors worldwide with high mortality rates. Circular homeodomain-interacting protein kinase 3 (circHIPK3) is a highly abundant and stable circular RNA and have garnered signifi...Digestive system tumors are the most common tumors worldwide with high mortality rates. Circular homeodomain-interacting protein kinase 3 (circHIPK3) is a highly abundant and stable circular RNA and have garnered significant attention in the field of cancer research. This review systematically explores potential of circHIPK3 as a clinical biomarker, clinical significance in pharmacotherapy, and molecular mechanisms that regulate biological functions such as cell proliferation, survival, migration, invasion, epithelial-mesenchymal transition, metabolism and angiogenesis in digestive system tumors. Moreover, this review further explored the influence of circHIPK3 on key signaling pathways and the potential clinical value as a diagnostic biomarker and therapeutic target. By delving into the biological functions and molecular mechanisms of circHIPK3, this review aims to provide novel research directions and theoretical guidance for the identification of new therapeutic targets and the development of individualized treatment protocols for digestive system tumors.
Nail apparatus melanoma (NAM) is a specific type of cutaneous melanoma that develops in the nail apparatus of the hands and feet. The prognosis for metastatic NAM is poor due to a lack of fully effective systemic therapi...Nail apparatus melanoma (NAM) is a specific type of cutaneous melanoma that develops in the nail apparatus of the hands and feet. The prognosis for metastatic NAM is poor due to a lack of fully effective systemic therapies. However, the difficulty in obtaining a NAM model has hindered basic research aimed at discovering effective treatment strategies. In this study, we established a NAM cell line, named KS-NailMel-1, from a primary tumor located on the nail apparatus of the left ring finger of a 68-year-old Japanese female. The cells were successfully maintained for over 9 months, exhibiting a doubling time of 38.6 ± 1.94 h. KS-NailMel-1 displayed consistent growth, spheroid formation, and invasiveness, and was confirmed to be identical to the original tumor through short tandem repeat analyses, whole-exome sequencing, and immunohistochemistry. Western blotting of the cells demonstrated the protein expression of NECTIN4, which has recently attracted attention as a potential therapeutic target for melanoma. The KS-NailMel-1 cell line represents a valuable resource for basic and preclinical research on NAM, deepening our understanding of the tumor characteristics and facilitating the development of treatment strategies for this rare form of cancer.
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract caused by dysfunction of the immune system in genetically susceptible individuals. As current pharmacologic and surgical t...Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract caused by dysfunction of the immune system in genetically susceptible individuals. As current pharmacologic and surgical treatments remain suboptimal, increasing attention has been directed toward exosomes derived from mesenchymal stem/stromal cells (MSCs) as alternative therapeutic approaches. MSCs are multipotent stromal cells that can be isolated from various human tissues such as bone marrow, adipose, umbilical cord and periodontal ligament. Exosomes are cell-derived membrane-bound vesicles enclosing RNAs, proteins, growth factors, and cytokines. Previous studies indicate that the anti-inflammatory, immunomodulatory, and regenerative effects of MSCs are largely mediated by MSC-derived exosomes (MSC-Exos). Therefore, this review outlines current insights into the molecular mechanisms of MSC-Exos in IBD treatment to support the future development of MSC-Exos as a therapeutic strategy, thus providing novel observations into the clinical applications of MSC-Exos in IBD management.
Studying the mechanism of hematopoietic stem cells' generation from induced pluripotent stem cells in vitro can be useful for understanding embryonic hematopoiesis, as well as for the application of related cell therapy....Studying the mechanism of hematopoietic stem cells' generation from induced pluripotent stem cells in vitro can be useful for understanding embryonic hematopoiesis, as well as for the application of related cell therapy. This study aimed to delineate the process of the differentiation of induced pluripotent stem cells into hematopoietic stem cells' models and provide a theoretical basis and clinical value for the production of hematopoietic stem cells in vitro. We analyzed the differentiation model by single-cell dynamic transcriptome and glycosylation sequencing, which was divided into three differentiation stages based on the new-to-total RNA ratio and glycosylation level. Two differentiation fates were found in the pseudo-time, including hematopoietic development and other tissue development. Precursor hematopoietic cells with a high glycosylation level greatly expressed hematopoietic regulation and vascular endothelial genes, suggesting that glycosylation is associated with angiogenesis and hematopoietic regulation. The multiple differentiation events in the in vitro model are similar to those in hematopoietic development in vivo, including yolk sac hematopoiesis, cellular communication between non-potential hematopoietic subsets and potential hematopoietic subsets, gene expression, and temporal deviations in hematopoietic fate. Our study has revealed the similar hematopoiesis process in the differentiation model via single-cell dynamic RNA and glycosylation sequencing, which provides an important theoretical basis for the study of hematopoietic stem cell development.
Myxoid liposarcoma (MLPS) is a malignant tumor composed of uniform, round-to-ovoid cells and small lipoblasts embedded in a myxoid stroma containing branching capillaries. MLPS is characterized by the presence of fusion...Myxoid liposarcoma (MLPS) is a malignant tumor composed of uniform, round-to-ovoid cells and small lipoblasts embedded in a myxoid stroma containing branching capillaries. MLPS is characterized by the presence of fusion genes, primarily FUS::DDIT3, with EWSR1::DDIT3 identified in a subset of cases. Although multimodal therapies have improved outcomes for localized MLPS, the prognosis for recurrent or metastatic MLPS cases remains poor, underscoring the need for novel therapeutic strategies. Patient-derived cell lines are essential tools in cancer research, providing various opportunities for discovery to the researchers. However, publicly available MLPS cell lines are lacking, which hinders research on this disease. With this notion, we established an MLPS cell line, NCC-MLPS4-C1. NCC-MLPS4-C1 was derived from the surgically resected tumor of a 48-year-old male patient with MLPS. We performed molecular and phenotypic characterization and high-throughput drug screening to evaluate its potential as a preclinical model. Genetic analysis confirmed the presence of the FUS::DDIT3 fusion gene in the original tumor and NCC-MLPS4-C1. NCC-MLPS4-C1 demonstrated stable proliferation, in vitro spheroid-forming ability, and invasive characteristics. We demonstrated that NCC-MLPS4-C1 is applicable for the global experiments such as drug screening. In conclusion, we successfully established NCC-MLPS4-C1, a novel cell line derived from surgically resected tumor tissue. NCC-MLPS4-C1 will be useful for the cancer research, especially in which the cell lines are required for global experiments.
Cutaneous squamous cell carcinoma (CSCC) is the second most prevalent skin cancer with low metastatic potential; it poses significant morbidity challenges. CSCC possesses significant heterogeneity and the treatment prese...Cutaneous squamous cell carcinoma (CSCC) is the second most prevalent skin cancer with low metastatic potential; it poses significant morbidity challenges. CSCC possesses significant heterogeneity and the treatment presents a formidable challenge. To gain a clear insight into the diverse nature of these tumors, the development of an in vitro cell line model is essential. However, there are few cell lines that were established, and only one skin SCC cell line is available on the ATCC. In the present study, we established and characterized a novel ACSCC1 cell line from the advanced-stage treatment naïve cutaneous SCC originating from the forearm of the Indian patient. The keratin expression profile showed the epithelial origin of the cell line, ploidy and karyotyping revealed the hyperdiploid population; ACSCC1 showed an increased tumorigenic and metastatic potential. Further, our cell line showed higher invasive, migratory potential and epithelial-mesenchymal-transition (EMT). Additionally, the Transmission electron microscopy (TEM) results showed an aberrant mitochondrial morphology and reduction in the cellular junctions. Further, our whole genome sequencing (WGS) analysis showed mutations in the cancer-related genes. Overall, the novel ACSCC1 cell line can be used to decipher the molecular signaling in the cancer stem cells (CSCs); targeting the CSCs population may help in understanding the tumor recurrence.
The endothelial glycocalyx is a dynamic brush-like layer composed of proteoglycans and glycosaminoglycans, including heparan sulfate (HS) and hyaluronic acid (HA), and is an important regulator of vascular homeostasis. I...The endothelial glycocalyx is a dynamic brush-like layer composed of proteoglycans and glycosaminoglycans, including heparan sulfate (HS) and hyaluronic acid (HA), and is an important regulator of vascular homeostasis. Its structure (thickness ranges from 20 to 6450 nm in different species) not only provides a charge-selective barrier but also serves to anchor mechanosensors such as the glypican-1 (GPC-1)/caveolin-1 (CAV-1) complex and buffers shear stress. In severe acute pancreatitis (SAP), inflammatory factors promote the expression of matrix metalloproteinases (MMPs) and heparinases, which degrade syndecan-1 (SDC-1) and HS, while oxidative stress disrupts HA-CD44 binding, leading to increased capillary leakage and neutrophil adhesion. This degradation process occurs before the onset of multiple organ dysfunction syndrome (MODS), highlighting the potential of the glycocalyx as an early biomarker. More importantly, the regeneration of glycocalyx through endothelial cell synthesis of glycosaminoglycans (GAGs) and shear stress-driven SDC recycling provides therapeutic prospects. This review redefines the pathophysiology of severe acute pancreatitis-associated multiple organ dysfunction (SAP-MODS) by exploring the glycocalyx's central mechanistic role and proposes stabilizing glycocalyx structure as a potential strategy to prevent microcirculatory failure.
Lung cancer is still considered to be the leading cause of cancer-related death worldwide, and lung adenocarcinoma (LUAD) is the most common kind. KDEL Endoplasmic Reticulum Protein Retention Receptor 3 (KDELR3) is a cri...Lung cancer is still considered to be the leading cause of cancer-related death worldwide, and lung adenocarcinoma (LUAD) is the most common kind. KDEL Endoplasmic Reticulum Protein Retention Receptor 3 (KDELR3) is a critical regulator of the endoplasmic reticulum (ER) stress and the followed unfolded protein response (UPR) process, which are critical in tumor development. However, the role of KDELR3 in LUAD tumor progression remains poorly understood. In this work, we demonstrated that KDELR3 is significantly upregulated in LUAD tumor tissues and cell lines. Suppression of KDELR3 promoted the phosphorylation level of UPR-related pathways, PERK, and EIF2α in LUAD cell lines. The downregulation of KDELR3 promoted ER stress-induced cell apoptosis, decreased the protein expression of Bcl-2, and increased the protein expression of Bax in LUAD cells. Moreover, the knockdown of KDELR3 inhibits LUAD cell invasion. In vivo animal experiments confirmed that the inhibition of KDELR3 suppresses LUAD tumor growth and metastasis. Mechanistic studies showed that transcription factor FOXM1 may serve as an upstream factor of KDELR3. The upregulation of FOXM1 increased the transcriptional activity of KDELR3. Further results illustrated that FOXM1 directly binds to the promoter of KDELR3, thus upregulating its expression. Finally, rescue experiments demonstrated that FOXM1 inhibition-induced cell apoptosis and invasion could be reversed by KDELR3 overexpression. Overall, our findings indicated that KDELR3 is transcriptionally upregulated by FOXM1 and accelerates tumor growth and lung metastasis in LUAD by inhibiting ER stress-induced cell apoptosis.
Diabetic retinopathy is a retinal damage, which causes vision impairment and blindness. Integrin Subunit Alpha 5 (ITGA5) regulates angiogenic response, but its roles in diabetic retinopathy remain unclear. In this work,...Diabetic retinopathy is a retinal damage, which causes vision impairment and blindness. Integrin Subunit Alpha 5 (ITGA5) regulates angiogenic response, but its roles in diabetic retinopathy remain unclear. In this work, diabetes mellitus was induced in rats by streptozotocin. ITGA5 interference was achieved by intravitreal delivery of adeno-associated virus. Upregulation of ITGA5 was found in diabetic rat retinal tissues. ITGA5 knockdown decreased the neovascularization, acellular capillary formation, and pericytes. The protein expression of vascular endothelial growth factor (VEGFA), vascular adhesion molecule-1(VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) was reduced after ITGA5 interference. Besides, ITGA5 knockdown decreased the phosphorylation level of FAK, TAK-1, and p65. In vitro, rat retinal microvascular endothelial cells (RRMECs) were cultured under high glucose condition to stimulate diabetic environment. ITGA5 knockdown inhibited VEGFA secretion, tube formation, cell invasion, and migration. Upregulation of VCAM-1 and ICAM-1 that induced by high glucose was reversed by ITGA5 silencing. ITGA5 knockdown blocked the activation of TAK-1/NF-kB pathway in RRMECs. Additionally, in oxygen-induced retinopathy model, ITGA5 interference inhibited pathological neovascularization. These results demonstrate that ITGA5 contributes to the angiogenesis in diabetic retinopathy by activating TAK-1/NF-kB pathway.