TGFB1

Overview

TGFB1 encodes transforming growth factor beta-1 (TGF-β1), a secreted cytokine and multifunctional signaling molecule in the transforming growth factor beta family. It is a central regulator of cell growth, differentiation, extracellular matrix production, immune modulation, wound repair, and tissue remodeling. Through canonical Smad2/3 signaling and related non-canonical pathways, TGF-β1 can promote either homeostatic repair or pathological fibrosis depending on cellular context, dose, and disease state.

In biomedical research, TGFB1 is frequently studied as both a mechanistic driver and a therapeutic target. It is especially relevant in fibrosis, cancer progression, immune suppression, cartilage regeneration, diabetic wound healing, and transplant biology. In tumors, TGFB1 is often associated with immunosuppressive microenvironments and poor prognosis; in regenerative settings, it can support matrix deposition and lineage-specific differentiation, including chondrogenesis and wound repair.

Focus of Latest Publications

Recent studies have examined TGFB1 across a broad range of disease contexts, often as part of signaling networks involving Smad2/3, VEGF, STAT3, IL6, PTGS2, CXCL9-CXCR3, and pathways linked to fibrosis, immune evasion, and tissue regeneration.

In hepatocellular carcinoma, spatial transcriptomics identified UBE2C-high regions within proliferative niches that showed immunosuppressive features, including TGFB1 enrichment, impaired CXCL9-CXCR3 signaling, and exclusion of cytotoxic T cells. These TGFB1-enriched regions were reduced in immunotherapy responders, supporting the idea that TGFB1 contributes to an immune-excluded tumor microenvironment.

In diabetic nephropathy, a systematic pharmacological evaluation of fermented Astragalus membranaceus broth (FA) identified TGFB1 as one of the core targets alongside STAT3 and IL6, with implicated pathways including AGE-RAGE, HIF-1, and FoxO. This places TGFB1 within a broader anti-inflammatory and anti-fibrotic network proposed for the fermented herbal preparation.

In cartilage engineering and chondrogenesis, TGFB1 was used as a pro-differentiation cue. In periosteum-derived cell spheroids embedded in HAMA hydrogels and bioprinted constructs, combination with TGF-β1 enhanced chondrogenesis, with stronger collagen fiber organization, increased glycosaminoglycan deposition, and positive Safranin O staining compared with material-free conditions. Similarly, a thermosensitive hydrogel system using hydroxybutyl chitosan and exosome-based delivery activated TGF-β1/Smad2/3 while suppressing Notch signaling, thereby promoting BMSC chondrogenic differentiation.

In fibrotic cardiovascular disease, TGFB1 was highlighted as a mediator of fibrosis in a diabetic cardiomyopathy rat model. The study on oleuropein reported that TGF-β1, acting through Smad2/3, promotes fibrotic gene expression, and that modulation of this pathway was associated with attenuation of cardiac fibrosis.

In pancreatic cancer, integrative multi-omics analysis found that high TGFB1 predicted poor prognosis in pancreatic ductal adenocarcinoma, consistent with its established association with aggressive disease biology and stromal remodeling.

In diabetic wound healing, TGFB1 appeared in multiple regenerative contexts. A functional hyaluronic acid/gelatin/poly(N-isopropyl acrylamide) hydrogel was reported to upregulate pro-healing mediators including TGF-β1, α-SMA, and p-Smad2, supporting wound closure and repair. Another study using a decellularized dermal scaffold with adjunct biophysical stimulation found elevated TGF-β1 and VEGF, with maximal expression in the combined treatment group, indicating enhanced pro-regenerative signaling.

TGFB1 was also targeted in tumor immunotherapy engineering. In colon carcinoma-derived extracellular vesicles, investigators used lentiviral modification to overexpress IL-18 and/or knock down TGF-β1 or IL-10 to improve the immunogenic potential of tumor extracellular vesicles for next-generation dendritic cell vaccines. This reflects a strategy to reduce TGFB1-mediated immunosuppression while increasing antigenic stimulation.

In osteosarcoma, Liquidambaris fructus was reported to inhibit tumor progression through PTGS2/TGFB1 and regulation of efferocytosis, suggesting TGFB1 is part of the inflammatory and tumor-supportive circuitry being pharmacologically modulated.

In kidney transplantation, exposure of proximal tubular epithelial cells to TGF-β1 reduced miR-7975 expression in urinary exosomes, implicating TGF-β1-responsive tubular cells as a potential source of exosomal biomarkers associated with subclinical acute T-cell-mediated rejection.

Finally, in a study of diabetic wound repair, a hydrogel-based system was associated with increased TGF-β1 signaling, while another scaffold-based approach similarly elevated TGF-β1 and VEGF. Together, these studies reinforce TGFB1 as a key mediator of matrix remodeling, angiogenesis, and tissue repair.

Across these reports, TGFB1 emerges as a context-dependent regulator: it can support fibrosis and immune escape in cancer and chronic disease, yet also promote repair, matrix formation, and lineage differentiation in regenerative medicine.

Key Publications

• Jun Superior In Vivo Efficacy of Fermented Over Aqueous Astragalus membranaceus in Diabetic Nephropathy: A Systematic Pharmacological Evaluation and Mechanistic Study. (Biomedical chromatography : BMC, 2026, PMID 42009593): "Chemical profiling identified 14 FA bioactive components; network pharmacology revealed core targets (STAT3, IL6, and TGFB1) and key pathways (AGE-RAGE, HIF-1, and FoxO)."
• May Chondrogenic differentiation of human periosteum-derived cells in spheroids, HAMA hydrogels, and bioprinted constructs: comparison of kartogenin and TGF-β1. (Biomedical materials (Bristol, England), 2026, PMID 42102888): "When combined with TGF-β1, HAMA-encapsulated spheroids showed enhanced chondrogenesis, as evidenced by stronger collagen fiber organization, increased glycosaminoglycan deposition, and positive Safranin O staining, absent in material-free conditions."
• May Integrative multi-omics and experimental validation reveal UBE2C as a central hub gene and prognostic biomarker in hepatocellular carcinoma. (International immunopharmacology, 2026, PMID 42155390): "Spatial transcriptomics highlighted UBE2C-high regions within proliferative niches exhibiting immunosuppressive traits-including TGFB1 enrichment, impaired CXCL9-CXCR3 signalling, and exclusion of cytotoxic T cells-which were reduced in immunotherapy responders."
• May Oleuropein attenuates cardiac fibrosis via modulation of TGF-β1/Smad pathway in diabetic cardiomyopathy rat model. (Scientific reports, 2026, PMID 42151222): "Transforming growth factor beta-1 (TGF-β1), via Smad2/3 signaling pathway, promotes fibrotic gene expression."
• May Integrative multi-omics analysis identifies a core ferroptosis signature and validates resveratrol as a novel inducer in pancreatic cancer. (Naunyn-Schmiedeberg's archives of pharmacology, 2026, PMID 42142137): "Clinical validation revealed high CTSB/TFRC protein expression in PDAC; high TGFB1 predicted poor prognosis."
• May Functional hyaluronic acid/gelatin hydrogel accelerates the closure and healing of diabetic wounds. (Carbohydrate polymers, 2026, PMID 41831972): "...and upregulate the expression of pro-inflammatory factors TGF-β1, α-SMA, and p-Smad2, all of which could aid in the healing process of diabetic wounds."
• May Modulation of angiogenic, inflammatory, and matrix remodeling responses in type 2 diabetic wounds by a decellularized dermal scaffold and adjunct biophysical stimulation. (Histochemistry and cell biology, 2026, PMID 42133132): "At the molecular level, treated wounds displayed elevated levels of pro-regenerative mediators, including transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF), with maximal expression observed in the combined group."
• May Identification of Urinary Exosomal microRNAs Associated With Subclinical Acute T-Cell-Mediated Rejection in Kidney Transplant Recipients. (Clinical and translational science, 2026, PMID 42067915): "In vitro, exposure of proximal tubular epithelial cells to transforming growth factor-beta 1 resulted in a reduction in miR-7975 expression within urinary exosomes, implicating these cells as a potential source of exosomal miR-7975."
• May Liquidambaris fructus inhibits osteosarcoma through PTGS2/TGFB1 and regulates efferocytosis. (Pakistan journal of pharmaceutical sciences, 2026, PMID 41879412): "Liquidambaris fructus inhibits osteosarcoma through PTGS2/TGFB1 and regulates efferocytosis."
• Apr Functionalized Thermosensitive Hydrogel Regulates the Immune Microenvironment and Stem Cell Differentiation to Enhance Cartilage Regeneration. (ACS nano, 2026, PMID 41969062): "Mechanistically, HBC@Sr@CPC-EXOs activated TGF-β1/Smad2/3 while suppressing Notch, driving bone marrow stromal cell (BMSC) chondrogenic differentiation."