growth factors TGF-β1 and VEGF

Overview

Transforming Growth Factor Beta 1 (TGF-β1) and Vascular Endothelial Growth Factor (VEGF) are pivotal proteins involved in various biological processes, including cell growth, differentiation, and angiogenesis. TGF-β1 is a multifunctional cytokine that plays a crucial role in regulating immune responses, cellular proliferation, and extracellular matrix production. It is particularly significant in fibrosis and tissue repair mechanisms. VEGF, on the other hand, is a key regulator of angiogenesis, promoting the formation of new blood vessels from pre-existing ones, which is essential for normal development and wound healing. Both growth factors are implicated in numerous pathological conditions, including cancer, diabetes, and cardiovascular diseases.

Focus of Latest Publications

Recent publications examined TGF-β1 and VEGF modulation across multiple disease contexts, employing both inhibitory and delivery-based strategies. VEGF inhibition approaches—including monoclonal antibodies (bevacizumab, ranibizumab), VEGF receptor antagonism, VEGF-targeting siRNA, and bispecific antibodies co-targeting VEGF and immune checkpoints—were evaluated in retinal pathology, diabetic kidney disease, hepatocellular carcinoma, ovarian cancer, and advanced lung cancer. In neovascular age-related macular degeneration and diabetic retinopathy, VEGF suppression preserved retinal morphology, restored visual function, and suppressed pathological angiogenesis. In diabetic kidney disease, selective VEGF receptor 1 blockade conferred renoprotection, clarifying prior conflicting outcomes from broader VEGF inhibition. In ovarian cancer, bevacizumab resistance was mechanistically driven by lactate-induced lactylation of enolase 1, which epigenetically upregulated pro-angiogenic factors and maintained vascular support despite anti-VEGF therapy.

In contrast, other studies engineered VEGF delivery systems for regenerative purposes. Hydrogel platforms incorporating dynamic VEGF loading promoted vascular endothelial growth and tissue integration in nerve and tracheal engineering. Patient-derived tumor organoid co-cultures elevated VEGF secretion, which was suppressed by bevacizumab treatment, enabling time-resolved assessment of anti-angiogenic responses in personalized cancer models.

TGF-β1 pathway inhibition emerged as a central therapeutic strategy in fibrotic and malignant diseases. Across idiopathic and bleomycin-induced pulmonary fibrosis and diabetic kidney disease, TGF-β1/Smad signaling suppression—via small-molecule inhibitors, siRNA knockdown, and botanical compounds—reduced fibrosis severity, restored organ function, suppressed epithelial-mesenchymal transition, attenuated oxidative stress, and improved mitochondrial dysfunction. In hepatocellular carcinoma, TGF-β1 activation through the YEATS2-TAK1 axis mediated adaptive sorafenib resistance, while in peritoneal and wound contexts, TGF-β1 drove fibroblast activation and mesenchymal transition. A dual-targeted nanoparticle platform simultaneously suppressed the hypoxia-inducible factor-1α/VEGF axis and TGF-β1-mediated fibrosis in tumor microenvironments, suggesting synergistic benefit from inhibiting both pathways.

Integrated approaches targeting both VEGF and immune regulation showed enhanced efficacy. A bispecific antibody binding PD-1 and VEGF demonstrated superior progression-free survival in advanced squamous lung cancer compared to conventional checkpoint inhibitors, while PD-1/VEGF dual imaging probes enabled noninvasive assessment of immune-vascular crosstalk in tumors. Collectively, these findings position TGF-β1 and VEGF as versatile therapeutic targets, where pathway suppression addresses fibrosis and malignant progression, while controlled delivery supports tissue regeneration and vascularization across regenerative medicine, fibrotic disease, and oncology contexts.

Key Publications

• NEWJun Deletion of CEACAM1 does not affect retinal and choroidal morphology or transcriptome. (Cell and tissue research, 2026, PMID 42360388): "CEACAM1 (CC1) is an important mediator of cell proliferation and adhesion and serves as an angiogenic factor through interaction with VEGF."
• NEWJun Bridging the gap: towards a digital twin to optimize therapeutic cell-seeding strategies in nerve tissue engineering. (Journal of the Royal Society, Interface, 2026, PMID 42336395): "We evaluate the regenerative potential of these designs by focusing on the impact of different cell-seeding strategies on vascular endothelial growth factor secretion and gradient generation, both crucial elements of regenerative angiogenesis in early nerve repair."
• NEWJul Resolving the VEGF paradox in DKD: VEGFR1 blockade shows promising renoprotection. (Kidney international, 2026, PMID 42315235): "selective modulation of the vascular endothelial growth factor (VEGF) system differentially affects diabetic kidney disease progression across multiple advanced diabetic models."
• Jun Plasticizer-responsive molecular axes in heart failure: a subtype-aware toxicogenomic framework relevant to environmental health. (Environment international, 2026, PMID 42235321): "Integrative analyses suggested associations between plasticizer clusters and HF-relevant pathogenic axes, including inflammatory remodeling, metabolic stress, and extracellular matrix processes, with subtype-resolved enrichment patterns consistent with VEGF/MAPK and hormonal signaling in dilated cardiomyopathy (DCM) and TNF/IL-17 and the diabetes-associated AGE-RAGE axis in ischemic cardiomyopathy (ICM)."
• May Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in advanced squamous non-small-cell lung cancer (HARMONi-6): interim overall survival analysis of a randomised, double-blind, phase 3 trial in China. (Lancet (London, England), 2026, PMID 42218899): "Bispecific antibodies targeting programmed death 1 (PD-1) and vascular endothelial growth factor (PD1-VEGF) have shown promising efficacy in non-small-cell lung cancer (NSCLC)."
• May Engineering RVG-modified exosomes for targeting TGF-β1 signaling in stroke recovery. (Journal of translational medicine, 2026, PMID 42215998): "To investigate the role of TGF-β1 signaling in astrocyte-neuron interactions after ischemic stroke and to develop a brain-targeted engineered exosome system, EXO-RVG-SD208, for promoting neural repair."
• May Vasant Kusumakar Rasa reduces neovascularisation, oxidative stress, inflammation and improves retinal function in diabetic rats. (Journal of molecular histology, 2026, PMID 42209874): "Expression of MMP-2 and VEGF was studied in eye."
• May Ameliorative effects of bevacizumab against sepsis-induced acute kidney injury: investigation of inflammatory responses, pyroptosis-related signalling and angiogenesis in a murine model of polymicrobial sepsis. (Molecular biology reports, 2026, PMID 42201618): "Bevacizumab is a biopharmaceutical agent that disrupts the angiogenesis signalling pathway by binding to vascular endothelial growth factor (VEGF) and preventing it from coupling with cognate receptors."
• Jun Pirfenidone Elevates GLIS1 by Disrupting the USP7/DNMT1 Complex and Alleviates Renal Fibrosis in Diabetic Kidney Disease Through ROS Reduction and TGF-β1/Smad Signaling Inhibition. (FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2026, PMID 42159303): "PFD alleviated renal injury and fibrosis in DKD rats by suppressing TGF-β1/Smad signaling."
• May ENO1 lactylation drives bevacizumab resistance through metabolic reprogramming and angiogenesis in ovarian cancer. (Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy, 2026, PMID 42134086): "Bevacizumab, a monoclonal antibody targeting Vascular Endothelial Growth Factor (VEGF), is a cornerstone therapy for ovarian cancer (OC)."