作者: Qiao, Tian ; Li, Chun-Xiao ; Ge, Wei ; Qiao, Zhan-Zhong ; Han, Qian-Ru ; Ruan, Gui-Li ; Cheng, Shun-Feng ; Xu, Chang ; Shen, Wei ; Wang, Ping ; Liu, Yong-Chao ; Zhang, Ying

Skin-derived stem cells (SDSCs) are a subtype of adult stem cells (ASCs). How to improve the self-renewal ability of stem cells has been a focus of recent research. However, the underlying self-renewal mechanism of SDSCs remains to be fully understood. Here, this study investigates the mechanism by which TET1 functions in the self-renewal of porcine SDSCs (pSDSCs). The results showed that the self-renewal capacity of pSDSCs gradually enhanced and the expression level of TET1 significantly increased during in vitro culture. Additionally, the self-renewal capacity of pSDSCs was inhibited after silencing TET1 by small interfering RNA (siRNA). RNA-seq analysis revealed that TET1 knockdown significantly inhibited the transforming growth factor-β (TGF-β) signaling pathway. Detailed analysis of key molecules in the TGF-β signaling pathway indicated that TET1 knockdown reduced the protein levels of TGF-β1, phosphorylated SMAD2 (p-SMAD2), and phosphorylated SMAD3 (p-SMAD3). SRI-011381, activated the TGF-β/SMAD pathway, saving the self-renewal defect caused by TET1 knockdown. Treating pSDSCs with LY2109761, a TGF-β signaling inhibitor, produced a phenotype similar to TET1 knockdown. This work identified that TET1 was a critical regulatory factor that plays a key role in maintaining pSDSCs self-renewal through the TGF-β signaling pathway. Unlike previous studies that primarily emphasized the epigenetic role of TET1, this study reveals its functional link to a signaling pathway. These findings provide a deeper understanding of SDSCs and suggest that targeting the TET1-TGF-β axis may represent a promising approach to enhance the self-renewal capacity of SDSCs.

2025-12-01·JOURNAL OF MOLECULAR HISTOLOGY

Butein attenuates cardiac fibrosis by mediating TGF-β1/Smad signaling pathway after myocardial infarction

Article

作者: Ma, Rui ; Lu, Pan ; Guo, Xin ; Li, Jinlei ; Tan, Rong ; Deng, Mengmeng ; Chen, Zhen

BACKGROUND:

Myocardial fibrosis has been found to accelerate heart dysfunction after myocardial infarction (MI). Butein is a chalcone compound possessing multiple biological properties. However, its effect on MI-induced myocardial fibrosis remains unclear.

METHODS:

A mouse MI model was established by left anterior descending ligation. Human cardiac fibroblasts (HCFs) were stimulated with TGF-β1 in vitro. Mouse cardiac function was evaluated by assessing EF and FS. Masson's trichrome staining showed the fibrosis area in murine hearts. Western blotting evaluated protein levels of fibrosis markers and signaling-related markers. CCK-8, EdU, and Transwell assays were used to evaluate HCF proliferation and migration.

RESULTS:

Butein improved MI-induced cardiac dysfunction and reduced the fibrosis area in mice. Butein inactivated TGF-β1/Smad signaling in MI mice and TGF-β1-stimulated HCFs. Butein inhibited TGF-β1-induced proliferation, migration, and collagen synthesis in HCFs, which were similar to the effects of LY2109761, a pharmacological inhibitor of TGF-β signaling.

CONCLUSION:

Butein mitigated MI development by inhibiting cardiac fibrosis and ECM deposition by inactivating the TGF-β1/Smad signaling pathway.

2025-12-01·APPLIED RADIATION AND ISOTOPES

Role of the TGF-β/SMAD pathway in tumor radioresistance to boron neutron capture therapy (BNCT) in a human cell line of colon adenocarcinoma

Article

作者: Perona, Marina ; Pastini, Antonella ; Rossich, Luciano ; Thomasz, Lisa ; Carpano, Marina ; Nievas, Susana ; Pavlik, Estanislao ; Thorp, Silvia ; Dagrosa, María Alejandra ; Peralta, Tomas ; Curotto, Paula

BNCT is a radiotherapeutic modality of high LET energy for different solid tumors as colorectal carcinoma (CRC). Although clinical outcomes show advantages of BNCT, tumor recurrence remains a common challenge. Previously we have described the double strand DNA damage response (DDR) produced by BNCT. TGF-β/SMAD pathway has been involved in maintaining genomic integrity. The aim of these studies was to evaluate the activation of the TGF-β/SMAD pathway, its interaction with the DDR pathway and the possible use of LY2109761 (Ly), a specific inhibitor of TGF-β receptor, as a radiosensitizer for BNCT. Six groups were performed in a human colon adenocarcinoma (HT29) cell line: NCT (neutrons), BNCT (boronophenylalanine plus neutrons), Control and the same three groups with the addition of Ly. The results showed an activation of the TGF-β/SMAD cascade with an increase in the genomic expression of TGF-β, SMAD7 and ATR (p < 0.001) at 2 h post neutron treatments compared to the Control group. A significant decrease in the expression of TGF-β receptor type I, SMAD7 and ATR for BNCT plus Ly was observed. Furthermore, it was demonstrated a decrease in tumor survival as a function of the total absorbed physical dose for all the treatments, being significantly higher in the groups treated with Ly at 1 and 3 Gy. On the other hand, a lower number of Ki67+ cells with the addition of Ly was found. Conclusion: The activation of the TGF-β/SMAD pathway and its interaction with the DNA repair via through ATR transductor was demonstrated. LY2109761 could act as a radiosensitizer for BNCT.

100 项与 LY-2109761 相关的药物交易

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