growth factors TGF-β1 and VEGF

Overview

Transforming Growth Factor Beta 1 (TGF-β1) and Vascular Endothelial Growth Factor (VEGF) are secreted signalling proteins — growth factors that bind cell-surface receptors to regulate tissue growth, remodelling and blood vessel formation. They are distinct proteins from separate families, grouped here because they are frequently studied together as paired mediators of injury, repair and vascular pathology. TGF-β1 is a multifunctional cytokine secreted in a latent form and activated extracellularly, after which it signals through TGF-β receptor complexes and SMAD proteins to suppress immune activation, drive fibroblast activation and extracellular matrix deposition, and promote epithelial-to-mesenchymal transition — a programme linked to EGFR/SRC-mediated EMT and to matrix turnover involving enzymes such as matrix metalloproteinase-2 (MMP-2). Its role in fibrosis and tissue repair extends to the central nervous system, where TGF-β1 signalling shapes astrocyte–neuron interactions during recovery from ischaemic stroke and can be targeted for neural repair.

VEGF is the principal driver of angiogenesis, binding VEGF receptor 1 and VEGF receptor 2 on endothelial cells to stimulate proliferation, migration and vascular permeability; it is required for normal development and wound healing and can be modulated by partners such as CEACAM1 on endothelial and myeloid cells. Because pathological neovascularisation underlies diabetic retinopathy, diabetic kidney disease and tumour growth, VEGF is among the most heavily exploited drug targets in medicine. Monoclonal antibodies including bevacizumab and Ranibizumab sequester VEGF, VEGFR tyrosine kinase inhibitors such as sorafenib block downstream receptor signalling, and bispecific antibodies now pair VEGF blockade with immune checkpoint inhibition against PD-1 and PD-L1 in Cancers such as non-small-cell lung cancer and ovarian cancer. Receptor selectivity matters: VEGF-A or VEGF receptor 2 inhibition can worsen albuminuria in diabetic kidney disease, whereas VEGF receptor 1 blockade appears renoprotective. Both growth factors also operate alongside oxidative stress and proinflammatory cytokines such as interleukin 17A (IL-17A) in conditions ranging from sepsis-associated acute kidney injury to heart failure.

Recent Publications Summary

Recent publications examined growth factors TGF-β1 and VEGF mainly as mechanistic targets in fibrosis, angiogenesis, and tissue repair. In diabetic kidney disease, pirfenidone was reported to alleviate renal injury and fibrosis by suppressing TGF-β1/Smad signaling, while a separate study found that dual siRNA knockdown of Alox15 and TGF-β1 delivered by lipid nanoparticle improved lung function and reduced fibrosis severity in bleomycin-induced pulmonary fibrosis 42159303May41847300Mar. In pulmonary fibrosis, other work linked TGF-β1 to profibrotic signaling in models of paraquat-induced disease and TGF-β1-induced profibrotic responses, reinforcing its role as a central mediator of fibrotic remodeling 41085213Oct41713661Feb. In abdominal wall reconstruction, a TGF-β receptor inhibitor-loaded mesh suppressed TGF-β1 secretion, epithelial-mesenchymal transition, and pro-fibrotic responses, reducing mesh contraction in rats 41935720Apr.

VEGF-focused studies largely centered on pathological angiogenesis and anti-VEGF intervention. In retinal disease, a retina-targeted exosome-liposome hybrid system delivering VEGF-silencing siRNA achieved potent VEGF knockdown, inhibited endothelial cell proliferation, and suppressed choroidal neovascularization in vivo 42093552May. In diabetic retinopathy, Vasant Kusumakar Rasa reduced neovascularisation and altered VEGF expression in the eye of diabetic rats 42209874May. In sepsis-induced acute kidney injury, bevacizumab was evaluated as a VEGF-binding agent for renoprotection 42201618May, while in ovarian cancer, bevacizumab resistance was linked to ENO1 lactylation and enhanced angiogenesis 42134086May. Additional work in diabetic kidney disease highlighted the importance of selective VEGF pathway modulation, reporting that VEGF-A or VEGFR2 inhibition worsened albuminuria whereas VEGFR1 blockade was renoprotective 42315235Jun.

Several studies used VEGF as a readout or engineering goal in regenerative and imaging platforms. A digital-twin approach for nerve tissue engineering optimized cell-seeding strategies by focusing on VEGF secretion and gradient formation as key determinants of regenerative angiogenesis 42336395Jun. In tracheal reconstruction, a bioprinted graft incorporated dynamic VEGF loading and sustained release to promote endothelial migration and neovascularization 42102210May. A microfluidic PDO-endothelial co-culture system quantified VEGF dynamics alongside vascular network formation and showed that bevacizumab reduced both angiogenic metrics and VEGF accumulation 41764903Mar. For imaging and therapy monitoring, an 89Zr-labeled PD-1/VEGF bispecific probe enabled dual-targeted immuno-PET of VEGF and PD-1 in tumors 42026833Apr, and a PD-1/VEGF bispecific antibody was also evaluated in advanced squamous non-small-cell lung cancer 42218899May.

What Changes, What Holds

1. TGF-β1 remains a central profibrotic target, with new delivery and combination strategies strengthening rather than revising that role
REINFORCES Recent work keeps TGF-β1 aligned with the Overview’s account of fibrosis and tissue repair, showing that suppressing TGF-β1/Smad signaling can lessen renal and pulmonary injury and that local receptor blockade can reduce epithelial-mesenchymal transition and mesh contraction 42159303May41935720Apr. The main change is practical: the target looks increasingly actionable across organs, but the underlying mechanism is the same one already established.

2. VEGF blockade and VEGF readouts are being pushed into more disease settings, but the core angiogenesis model stands
REINFORCES These studies extend the established VEGF story into retinal neovascular disease, sepsis-associated kidney injury, ovarian cancer resistance, and diabetic kidney disease, while still relying on the same basic premise that VEGF drives pathological angiogenesis and vascular leakage 42093552May42315235Jun. What is added is not a new biology but sharper evidence that selective pathway choice matters, especially where VEGF-A/VEGFR2 inhibition may worsen albuminuria and VEGFR1 blockade may be safer.

3. VEGF is increasingly useful as both a therapeutic target and a quantitative engineering signal
METHOD Digital-twin optimization, bioprinted graft design, microfluidic co-culture, and dual-target imaging shift VEGF from a purely disease mediator to a measurable design variable and monitoring biomarker 42336395Jun42026833Apr. These studies do not revise the Overview’s biology; they change how VEGF is studied and deployed, especially in regenerative platforms and treatment tracking, while still using anti-VEGF effects as the expected readout.

Overview update candidates: selective VEGF pathway modulation in diabetic kidney disease; VEGF as a design/monitoring variable in regenerative and imaging platforms.