transforming growth factor-beta

Overview

Transforming growth factor-beta (TGF-β) is a multifunctional cytokine family with broad roles in cell growth, differentiation, extracellular matrix production, immune regulation, and tissue repair. In biomedical research, TGF-β is especially important because it can act as a context-dependent regulator: in some settings it supports normal homeostasis and wound healing, while in others it contributes to fibrosis, immune suppression, epithelial-to-mesenchymal transition, and tumor progression. Its signaling is commonly discussed together with the Smad pathway, as well as non-canonical routes such as MAPK signaling.

In disease biology, TGF-β is frequently implicated in fibrotic disorders, chronic kidney disease, pulmonary arterial hypertension, tracheal scarring, myocardial fibrosis, and tumor microenvironment remodeling. It also intersects with immune cell differentiation and function, including regulatory T cells, natural killer cells, B cells, macrophages, and neutrophil biology. Because of this dual biology, TGF-β is both a mechanistic biomarker and a therapeutic target in oncology, fibrosis, and immunomodulation.

Recent Publications Focus

Below is a summary of the newest research publications targeting transforming growth factor-beta (sorted by publication date).

Recent publications have continued to position transforming growth factor-beta (TGF-β) as a central node in cancer, fibrosis, and immune regulation, while also highlighting new therapeutic strategies aimed at modulating this pathway. A review on TGF-β-targeted drug development described the field’s shift from traditional occupancy-based kinase inhibitors toward event-driven targeted protein degradation, including PROTACs and LYTACs, and emphasized medicinal chemistry approaches such as linker rigidification, tissue-specific E3 ligase selection, and the use of artificial intelligence and molecular docking to improve degrader design. In oncology, TGF-β was also discussed as a contributor to immune evasion and poor immune-cell penetration in recurrent or metastatic head and neck squamous cell carcinoma, and as a target in immune modulatory vaccines and bifunctional fusion proteins designed to remodel the tumor microenvironment.

Several studies focused on TGF-β-driven tumor progression and immune suppression. In EGFR-mutant lung cancer, TGF-β inhibition with nintedanib or vactosertib potentiated osimertinib-induced antitumor immunity in a syngeneic mouse model, increasing effector T cells and Granzyme B-positive areas while decreasing CD206-positive cells and TGF-β/SMAD2/3 expression. In Ewing sarcoma, TGF-β1-imprinted natural killer cells were used to circumvent TGF-β-mediated NK-cell immunosuppression in a combinatorial immunotherapy approach that also included IL1RAP CAR targeting, an IL-15 agonist, and anti-GD2 antibody. Other cancer-focused work linked TGF-β signaling to epithelial-to-mesenchymal transition, including a single-cell drug-response analysis that identified TGF-β-associated EMT signatures in resistant tumor states and a hydrophobic tag-based JNK1 degrader that inhibited TGF-β1-induced EMT.

Beyond cancer, multiple publications examined TGF-β in fibrotic disease and tissue remodeling. In liver fibrosis, cord-blood platelet-rich plasma attenuated fibrogenic features of TGF-β-activated hepatic stellate cells, reducing fibrosis-associated genes and proteins and suppressing migratory behavior in vitro while improving liver function and histopathology in vivo. In myocardial ischemia-reperfusion injury, Qishen Yiqi Dripping Pills were reported to alleviate fibrotic injury by inhibiting fibroblast activation through the TGF-β/Periostin pathway. In pulmonary fibrosis, an inhalable biomimetic nanodelivery system reduced profibrotic signaling linked to TGF-β by silencing ADORA2B and activating Nrf2, thereby decreasing macrophage infiltration and fibrosis in mice. Additional studies described TGF-β involvement in chronic colitis-associated intestinal fibrosis, atherosclerosis-related endothelial-to-mesenchymal transition, tracheal scar formation, diabetic kidney disease, and radiation-induced fibrosis in pancreatic ductal adenocarcinoma, where stromal reprogramming and reduced TGF-β-associated fibrogenic markers were associated with improved immune infiltration and treatment response.

Other recent reports highlighted TGF-β as a mediator of metabolic and inflammatory programs. In intrahepatic cholangiocarcinoma, miR-7-5p suppressed TGF-β-induced glycolysis and proliferation by targeting MyD88, with TGF-β activation reversing the inhibitory effects of MyD88 knockdown. In ox-LDL-treated macrophages, curcumin reduced P2X7R, NOX1, MMP-3, and TGF-β expression and limited foam cell formation, supporting an anti-atherosclerotic mechanism. In Duchenne muscular dystrophy, a mitochondria-targeted engineered peptide reduced inflammation and fibrosis while lowering TGF-β expression. Across these studies, TGF-β repeatedly emerged as a pathway linked to fibrosis, immune exclusion, EMT, and metabolic reprogramming, making it a recurring target for both direct inhibition and broader microenvironmental reprogramming strategies.

Background PMIDs

• [PMID 41792971]
• [PMID 41880834]
• [PMID 41956539]
• [PMID 41997282]
• [PMID 42090477]
• [PMID 42160453]
• [PMID 42309824]
• [PMID 42411223]

Result PMIDs

• [PMID 41335007]
• [PMID 41757675]
• [PMID 41819443]
• [PMID 41844050]
• [PMID 41967213]
• [PMID 42008225]
• [PMID 42033075]
• [PMID 42037322]
• [PMID 42061629]
• [PMID 42066974]
• [PMID 42141999]
• [PMID 42161228]
• [PMID 42204756]
• [PMID 42324293]
• [PMID 42329344]

Target PMIDs

• [PMID 41455284]
• [PMID 41587524]
• [PMID 41671386]
• [PMID 41702227]
• [PMID 41740333]
• [PMID 41757675]
• [PMID 41844050]
• [PMID 41856067]
• [PMID 41866914]
• [PMID 41875825]
• [PMID 41963297]
• [PMID 41992617]
• [PMID 42012656]
• [PMID 42102329]
• [PMID 42107578]
• [PMID 42222959]
• [PMID 42229655]
• [PMID 42269799]
• [PMID 42313121]
• [PMID 42341856]
• [PMID 42361193]
• [PMID 42398968]
• [PMID 42400723]
• [PMID 42411223]