Explore studies of thymosin beta 4.
Thymosin peptides both increase and decrease TdT activity depending on the maturation stage, indicating they regulate multiple phases of T-cell development.
Hu, S K; Low, T L; Goldstein, A L · Animal Study
The paper argued that certain molecules made by immune cells can send signals directly to the brain. The authors named these 'immunotransmitters,' a new term for molecules that carry information from the immune system to the central nervous system (CNS). Examples include thymosin alpha 1 and thymosin beta 4 (peptides from the thymus gland), as well as ACTH (a stress hormone), TSH (thyroid hormone), and beta-endorphin (a natural painkiller) produced by lymphocytes (white blood cells). The review presented evidence that thymosin peptides can alter the hypothalamic-pituitary-adrenal (HPA) axis, which is the brain's master hormone control system. They also appeared to affect the gonadal (reproductive hormone) axis.
Hall, N R; McGillis, J P; Spangelo, B L; Goldstein, A L · Review
Normal thymosin alpha 1 levels were similar across all groups of women tested, regardless of their hormonal status. This peptide appears unaffected by estrogen. Thymosin beta 4 told a different story. Castrated women not receiving estrogen had reduced levels. Postmenopausal women on chronic estrogen therapy had even lower thymosin beta 4. Castrated women on estrogen also showed decreased levels. Normal women in the early follicular phase (low estrogen point of the menstrual cycle), women with premature ovarian failure, and postmenopausal women not on estrogen all had similar thymosin beta 4 levels. But the premature ovarian failure and postmenopausal groups showed wide variation, suggesting these are not uniform populations.
Suh, B Y; Naylor, P H; Goldstein, A L; Rebar, R W · Cross Sectional
Normal thymosin alpha 1 levels: 670 ± 163 pg/mL for males and 652 ± 162 pg/mL for females. Normal thymosin beta 4 levels: 974 ± 400 ng/mL for males and 889 ± 345 ng/mL for females. Note that beta 4 levels are about 1,000 times higher than alpha 1. In AIDS patients, 57% had elevated thymosin alpha 1 and 48% had elevated thymosin beta 4. But there was no correlation between the two peptides' levels in any group, including healthy controls. People with AIDS-related immune dysfunction (not full AIDS) showed a different pattern: 54% had elevated thymosin alpha 1 but only 15% had elevated thymosin beta 4. This suggests thymosin alpha 1 rises earlier in the disease process.
Naylor, P H; Friedman-Kien, A; Hersh, E; Erdos, M; Goldstein, A L · Cross Sectional
Thymosin beta 4 peaked early and declined with age. hCG challenge depressed thymosin beta 4. Testosterone modulated both thymosin beta 4 and alpha 1 levels. Castration altered the patterns.
Wise, T H · Animal Study
Beta-thymosins (thymosin beta-4 predominantly) regulate actin polymerization and exhibit wound healing, anti-inflammatory, angiogenic, and cardioprotective activities — a structurally and functionally distinct peptide family from thymosin alpha-1 with unique therapeutic potential.
Hannappel, E · Review
Thymosin beta 4 (Tβ4) promoted hair growth in multiple rat and mouse models, including a transgenic mouse that overexpresses Tβ4. The researchers identified the mechanism: Tβ4 stimulates follicle stem cell growth, migration, differentiation, and protease production. These are the same cellular processes Tβ4 is known to activate in wound healing — cell movement, new blood vessel formation, and tissue remodeling — applied specifically to hair follicle biology.
Philp, Deborah; St-Surin, Sharleen; Cha, Hee-Jae; Moon, Hye-Sung; Kleinman, Hynda K; Elkin, Michael · Animal Study
Thymosin beta 4 protected endothelial progenitor cells (EPCs) from damage caused by advanced glycation endproducts (AGEs) — toxic compounds that accumulate in diabetes. The mechanism works through a specific molecular pathway: thymosin beta 4 suppresses microRNA-34a, which in turn allows the anti-apoptotic protein Bcl-2 to remain active. When microRNA-34a was artificially increased or Bcl-2 was knocked down, the protective effect of thymosin beta 4 was abolished, confirming this pathway is essential. The protection manifested as improved cell survival, reduced programmed cell death (apoptosis), lower oxidative stress, and better mitochondrial function.
Chen, Qi; Shen, Zhida; Mao, Yanjun; Li, Qinfeng; Liu, Yu; Mei, Menghan; Qiu, Fuyu; Wang, Meihui · In Vitro
Thymosin beta-4 treatment activated human adipose-derived stem cells by upregulating PI3K/AKT/mTOR and MAPK/ERK signaling pathways. It also increased cell migration, sprouting from microbeads, and endothelial differentiation potential. In a dorsal window chamber model, the combination of thymosin beta-4 and stem cells produced significantly more microvessel branches than stem cells alone. In the ischemic hindlimb model, mice receiving both thymosin beta-4 and stem cells had improved blood flow recovery and less limb or foot loss compared to stem cells alone. This suggests the peptide primes the stem cells to be more effective at building new blood vessels.
Kim, Jong-Ho; Lim, I-Rang; Park, Chi-Yeon; Joo, Hyung Joon; Noh, Ji-Min; Choi, Seung-Cheol; Hong, Soon Jun; Lim, Do-Sun · Animal Study
Intranuclear precursors of thymic peptides are ubiquitous in somatic cells and may function as stress sensors, releasing immunologically active peptides as cellular distress signals.
Lunin, Sergey; Khrenov, Maxim; Glushkova, Olga; Parfenyuk, Svetlana; Novoselova, Tatyana; Novoselova, E · Review
Tβ4 promoted angiogenesis in CLI mice by upregulating VEGFA, Ang2, tie2, CD31, and α-SMA via Notch/NF-κB pathway activation, and reversed the effects of pathway inhibitors.
Lv, Shumin; Cai, Hongwen; Xu, Yifei; Dai, Jin; Rong, Xiqing; Zheng, Lanzhi · Animal
Thymosin beta-4 depletion disrupted epidermal adherens junction stability and planar cell polarity by altering perijunctional G/F-actin ratios, causing eyelid closure and hair follicle angling defects.
Padmanabhan, Krishnanand; Grobe, Hanna; Cohen, Jonathan; Soffer, Arad; Mahly, Adnan; Adir, Orit; Zaidel-Bar, Ronen; Luxenburg, Chen · Animal Study
Tβ4 at 10 ng/mL improved diabetic EPC migration, tubule formation, and angiogenic factor secretion in vitro, and increased capillary density in vivo, but only non-Tβ4-treated EPCs significantly improved left ventricular ejection fraction.
Poh, Kian Keong; Lee, Poay Sian Sabrina; Djohan, Andie Hartanto; Galupo, Mary Joyce; Songco, Geronica Gorospe; Yeo, Tiong Cheng; Tan, Huay Cheem; Richards, Arthur Mark; Ye, Lei · Animal Study
Tβ4-treated fat grafts showed superior volume retention, weight preservation, adipocyte viability, tissue integrity, and angiogenesis at 2, 4, and 12 weeks compared to controls, with enhanced microcirculation confirmed by DCE-MRI.
Qu, Yaping; Wang, Qian; Fu, Su; Guo, Xiaoshuang; Luan, Jie; Mu, Dali · Animal Study
Salivary proteome analysis revealed significant variations in thymosin beta-4, defensins, and other proteins between mastocytosis subtypes (cutaneous, systemic with/without skin lesions) and healthy controls.
Serrao, Simone; Firinu, Davide; Olianas, Alessandra; Deidda, Margherita; Contini, Cristina; Iavarone, Federica; Sanna, M Teresa; Boroumand, Mozhgan; Amado, Francisco; Castagnola, Massimo; Messana, Irene; Del Giacco, Stefano; Manconi, Barbara; Cabras, Tiziana · Observational
Tβ4 promotes neurological recovery through neurovascular remodeling, CNS plasticity enhancement, and modulation of Toll-like receptor/NF-κB inflammatory signaling pathways, with microRNA-mediated regulation.
Shomali, Navid; Baradaran, Behzad; Deljavanghodrati, Mina; Akbari, Morteza; Hemmatzadeh, Maryam; Mohammadi, Hamed; Jang, Yue; Xu, Huaxi; Sandoghchian Shotorbani, Siamak · Review
Thymosin beta-4 increased tight junction protein expression, reduced the F-actin to G-actin ratio, and significantly improved vascular permeability dysfunction caused by PrP(106-126) in human brain endothelial cells.
Song, Kibbeum; Han, Hye-Ju; Kim, Sokho; Kwon, Jungkee · In Vitro
Thymosin beta-4 loaded PLGA/PLA hybrid yarns provided sustained drug release for 28 days and showed additive effects on promoting human adipose-derived stem cell migration, proliferation, and tenogenic differentiation compared to unloaded scaffolds.
Wu, Shaohua; Zhou, Rong; Zhou, Fang; Streubel, Philipp N; Chen, Shaojuan; Duan, Bin · In_vitro
Tβ4-mediated corneal epithelial cell proliferation and migration are associated with increased extracellular ATP levels, P2X7 receptor-mediated calcium influx, and ERK1/2 phosphorylation. P2X7 antagonists blocked Tβ4-induced migration.
Yang, Heung-Mo; Kang, Shin Wook; Sung, Jihye; Kim, Kyeongsoon; Kleinman, Hynda · In_vitro
Tβ4 significantly reduced caspase-9, MMP-9 activity, hyaluronan, oxidative stress, and inflammation markers while restoring antioxidant levels in both pre-treatment and peri-ischemic treatment groups. Serum creatinine and BUN were significantly reduced (p<0.001).
Aksu, Ugur; Yaman, Onur M; Guner, Ibrahim; Guntas, Gulcan; Sonmez, Fuat; Tanriverdi, Gamze; Eser, Mediha; Cakiris, Aris; Akyol, Sibel; Seçkin, İsmail; Uzun, Hafize; Yelmen, Nermin; Sahin, Gulderen · Animal
Tmsb4x was identified via in vivo CRISPR screening as a promoter of DGC liver metastasis. It enhanced clonogenicity and anoikis resistance. E-cadherin deficiency upregulated Tmsb4x via Wnt signaling in stomach organoids.
An, Hyeok-Won; Kim, Si-You; Kwon, Jong-Wan; Seok, Sang-Hyuk; Woo, Sang-Ho; Kim, Dae-Yong; Park, Jun Won · Animal
Both endogenous and exogenous thymosin β4 activate hair follicle cycling, promote stem cell migration and differentiation, and increase hair growth rate in animal models.
Dai, Bai; Sha, Ri-Na; Yuan, Jian-Long; Liu, Dong-Jun · Review
Maternal TB4 treatment (6 mg/kg on days E14 and E17) increased newborn cranio-caudal length and accelerated development of lungs, heart, kidneys, cerebral cortex, and notochord compared to control newborns.
Faa, G; Piras, M; Mancuso, L; Coni, P; Pichiri, G; Orrù, G; Fanni, D; Gerosa, C; Cao, G; Taibi, R; Pavone, P; Castagnola, M · Animal
TMSB4X was the most upregulated secreted protein from contracting C2C12 myotubes by MS-based proteomics, and was acutely increased in plasma of exercising humans irrespective of insulin resistance status.
Gonzalez-Franquesa, Alba; Stocks, Ben; Borg, Melissa L; Kuefner, Michael; Dalbram, Emilie; Nielsen, Thomas S; Agrawal, Ankita; Pankratova, Stanislava; Chibalin, Alexander V; Karlsson, Håkan K R; Gheibi, Sevda; Björnholm, Marie; Jørgensen, Niklas Rye; Clemmensen, Christoffer; Hostrup, Morten; Treebak, Jonas T; Krook, Anna; Zierath, Juleen R; Deshmukh, Atul S · Mixed Methods (Proteomics, Human Observational, Animal, In Vitro)
In vitro-evolved peptides bind monomeric actin and functionally mimic thymosin beta-4, the natural actin-sequestering protein. These represent the first synthetic probes for monomeric actin.
Gübeli, Raphael J; Bertoldo, Davide; Shimada, Kenji; Gerhold, Christian B; Hurst, Verena; Takahashi, Yuichiro; Harada, Kai; Mothukuri, Ganesh K; Wilbs, Jonas; Harata, Masahiko; Gasser, Susan M; Heinis, Christian · In Vitro Study
TB4, a developmentally essential 43aa secreted peptide, demonstrates multiple cardiac regenerative capabilities via systemic administration in adult organisms. The concept proposes using developmental peptides to reactivate embryonic regenerative programs in aging organs.
Maar, Klaudia; Hetenyi, Roland; Maar, Szabolcs; Faskerti, Gabor; Hanna, Daniel; Lippai, Balint; Takatsy, Aniko; Bock-Marquette, Ildiko · Review
CircPIP5K1A was significantly elevated in endometriosis tissues and cells. Silencing circPIP5K1A suppressed proliferation, blocked cell cycle progression, increased apoptosis, and decreased migration and invasion. The mechanism: circPIP5K1A sponges miR-153-3p, relieving its suppression of TMSB4X (Thymosin beta-4 X-linked). Elevated TMSB4X then activates TGF-β signaling, promoting endometriosis progression. Inhibiting miR-153-3p reversed the effects of circPIP5K1A knockdown, confirming the regulatory axis.
Sun, Lin; Wei, Yan; Wang, Junli · In Vitro
Thymosin beta-4 (Tβ4) eye drops at both 0.05% and 0.1% concentrations improved all clinical measures of dry eye disease in mice within 7 days. The peptide increased tear production, reduced corneal staining (a measure of surface damage), restored goblet cells in the conjunctiva (which produce the protective mucus layer), and reduced cell death in the cornea and conjunctiva. The mechanism was anti-inflammatory: Tβ4 reduced inflammatory cytokine levels and CD4+ T cell infiltration by blocking NF-κB activation — the master inflammatory switch. Both doses were effective.
Zhai, Yanfang; Zheng, Xiaoxiang; Mao, Yunyun; Li, Kai; Liu, Yanhong; Gao, Yuemei; Zhao, Mengsu; Yang, Rui; Yu, Rui; Chen, Wei · Animal Study (Mouse Model)
Thymosin beta 4 (Tβ4) protected hippocampal neuronal cells (HT22) against the toxic effects of the prion protein fragment PrP (106-126). Tβ4 significantly reversed the drop in cell viability and the spike in reactive oxygen species (ROS) caused by PrP (106-126). It also reduced levels of apoptotic (cell death) proteins triggered by the prion fragment. Importantly, Tβ4 maintained a competitive balance of neurotrophic factors — specifically nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) — along with their receptors (p75, TrkA, and TrkB). This suggests Tβ4 protects neurons by working through the neurotrophic factor signaling pathway rather than simply blocking the toxic peptide directly.
Kim, Sokho; Choi, Jihye; Kwon, Jungkee · In Vitro
This review examines the role of thymosin beta 4 (Tβ4) in glomerular disease — conditions affecting the kidney's filtration units that are a major driver of chronic kidney disease. Tβ4, which naturally sequesters G-actin (a building block of the cell's structural skeleton), has demonstrated potent anti-inflammatory effects in experimental models of injury across multiple organs including heart, kidney, liver, lung, and eye. The review covers both endogenous Tβ4 (what the kidney naturally produces) and exogenous Tβ4 (administered as treatment), examining how each influences glomerular disease progression and the mechanisms behind these effects.
Mason, William J; Vasilopoulou, Elisavet · Review
Tβ4 knockout impaired Mauthner cell axon regeneration in zebrafish, while overexpression promoted it. The mechanism requires Tβ4-G-actin binding and promotes actin polymerization (not depolymerization as some models predicted). Axon regeneration length correlated negatively with the straight-tail escape deficit. Tβ4 overexpression restored rapid escape behavior.
Song, Zheng; Han, Along; Hu, Bing · Animal Study
Thymosin beta-4 resolves bacterial keratitis inflammation by activating 5-LOX and 12/15-LOX enzymes, generating specialized pro-resolving mediators (lipoxins, resolvins), and directly enhancing macrophage phagocytosis through SPM pathway activation.
Wang, Yuxin; Banga, Loveleen; Ebrahim, Abdul Shukkur; Carion, Thomas W; Sosne, Gabriel; Berger, Elizabeth A · Animal Study
Thymosin β4 primarily regulates microfilament formation and mitochondrial transfer in thymic epithelial cells, influencing the differentiation of double-negative (CD4⁻CD8⁻) and CD4 single-positive (CD3⁺TCRβ⁺CD4⁺CD8⁻) thymocytes through F-actin aggregation.
Ying, Yuyuan; Tao, Nana; Zhang, Fengjie; Wen, Xunuo; Zhou, Meiru; Gao, Jianli · In Vitro