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.