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1.
Front Immunol ; 15: 1404974, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919615

RESUMO

Foxp3+ regulatory T cells (Foxp3+ Treg) play a role in regulating various types of tumors, but uncertainty still exists regarding the exact mechanism underlying Foxp3+ Treg activation in gastrointestinal malignancies. As of now, research has shown that Foxp3+ Treg expression, altered glucose metabolism, or a hypoxic tumor microenvironment all affect Foxp3+ Treg function in the bodies of tumor patients. Furthermore, it has been demonstrated that post-translational modifications are essential for mature Foxp3 to function properly. Additionally, a considerable number of non-coding RNAs (ncRNAs) have been implicated in the activation of the Foxp3 signaling pathway. These mechanisms regulating Foxp3 may one day serve as potential therapeutic targets for gastrointestinal malignancies. This review primarily focuses on the properties and capabilities of Foxp3 and Foxp3+Treg. It emphasizes the advancement of research on the regulatory mechanisms of Foxp3 in different malignant tumors of the digestive system, providing new insights for the exploration of anticancer treatments.


Assuntos
Fatores de Transcrição Forkhead , Linfócitos T Reguladores , Microambiente Tumoral , Humanos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Microambiente Tumoral/imunologia , Animais , Transdução de Sinais , Neoplasias do Sistema Digestório/imunologia , Neoplasias Gastrointestinais/imunologia
2.
Int J Biol Macromol ; 209(Pt A): 1516-1525, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35452701

RESUMO

Elevated expressions of transforming growth factor ß1 (TGF-ß1) have been implicated in the pathogenesis of liver fibrosis, thus attenuating the excessive TGF-ß1's activity by TGF-ß1-binding peptide is an ideal strategy for the treatment of liver fibrosis. However, the application of small peptide as a pharmaceutical agent is obstacle due to difficult preparation and non-selective delivery. The I-plus sequences of circumsporozoite protein (CSP-I) possesses high affinity for heparan sulfate proteoglycans, which are primarily located on liver tissues. TGF-ß1-binding peptide P15 holds specific ability of binding to TGF-ß1. In this study, we describe an approach to efficiently preparing liver-targeting peptide P15-CSP-I, which is conjugation of the sequences of P15 to the N-terminus of CSP-I, from the cleavage of biological macromolecule SUMO-tagged P15-CSP-I. In vitro and ex vivo binding assay showed that P15-CSP-I specifically targeted to the hepatocytes and liver tissues. Moreover, P15-CSP-I inhibited cell proliferation, migration and invasion, and decreased fibrosis-related proteins expression in TGF-ß1-activated HSCs in vitro. Furthermore, P15-CSP-I ameliorated liver morphology and decreased the fibrosis responses in vivo. Taken together, P15-CSP-I may be a potential candidate for targeting therapy on liver fibrosis due to its high efficient preparation, specific liver-targeting potential and improved anti-liver fibrotic activity.


Assuntos
Proteoglicanas de Heparan Sulfato , Fígado , Fator de Crescimento Transformador beta1 , Animais , Proteoglicanas de Heparan Sulfato/metabolismo , Humanos , Fígado/metabolismo , Cirrose Hepática/patologia , Camundongos , Peptídeos/metabolismo , Ratos , Proteína SUMO-1/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
3.
Int J Biol Macromol ; 188: 941-949, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34389395

RESUMO

Truncated transforming growth factor-ß receptor type II (tTßRII) is a promising anti-fibrotic candidate because it attenuates excessive transforming growth factor-ß1 (TGF-ß1) and then blocks TGF-ß1 activity in hepatic fibrosis. However, its use has been greatly limited due to the fact that it is expensive to chemically synthesize and it does not specifically target to the lesion site. In this study, we describe that platelet-derived growth factor ß receptor (PDGFßR)-binding peptide BiPPB modified tTßRII (BiPPB-tTßRII) was prepared from the cleavage of SUMO-BiPPB-tTßRII by digestion with SUMO-specific protease. Moreover, compared to the unmodified tTßRII, the target protein BiPPB-tTßRII not only highly specific targeted activated hepatic stellate cells (HSCs) and fibrotic liver tissue, but also significantly inhibited the protein levels of fibrosis-related genes in TGF-ß1-induced HSC-T6 cells and CCl4-induced liver fibrosis in mice. Furthermore, BiPPB-tTßRII markedly ameliorated liver morphology, fibrotic responses and the damage of liver function in fibrosis animal. More importantly, BiPPB-tTßRII showed a much lesser extent in binding to quiescent HSCs and non-fibrotic liver tissue. Taken together, our results suggested that the target protein BiPPB-tTßRII, with its high specific fibrotic liver-targeting potential and its improved anti-fibrotic activity in liver fibrosis, may be a potential therapeutic agent for liver fibrosis.


Assuntos
Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Peptídeos/administração & dosagem , Peptídeos/uso terapêutico , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II/administração & dosagem , Animais , Tetracloreto de Carbono , Linhagem Celular Tumoral , Vetores Genéticos/metabolismo , Camundongos , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo
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