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.

2026-01-01·Advanced Healthcare Materials

Autocrine TGF‐β1 in Periodontal Ligament‐Derived Stem Cell Pellets Enhances Periodontal Regeneration in Class II Furcation Defects of Canine Models

Article

作者: Fang, Siya ; Ahmadi, Sina ; Gong, Yuxin ; Liang, Xiang ; Xu, Fangfang ; Na, Sijia ; Elayah, Sadam Ahmed ; Zhang, Zhou ; Yu, Ming ; Tu, Junbo ; Bai, Le

Abstract:

The Class II furcation defects present a significant challenge in periodontal treatment and pose a considerable risk to tooth survival. While scaffold‐free Periodontal ligament stem cells (PDLSCs)‐derived cell pellets (CP) and sheets (CS) aid regeneration, the molecular mechanisms and efficacy of PDLSC‐CP remain unclear, especially in large animals. This study investigates PDLSC‐CP's regenerative potential for Class II defects through in vitro and in vivo analyses. PDLSC‐CP demonstrated superior cell viability, improved the extracellular matrix (ECM) quality, enhanced biomechanical properties, and a greater potential for periodontal tissue regeneration compared to PDLSC‐CS in both in vitro and in vivo scenarios. Importantly, autocrine transforming growth factor‐β1 (TGF‐β1) in PDLSC‐CP upregulated odonto/osteogenesis‐related factors by activating the TGF‐β1/Smad pathway. However, LY2109761, an inhibitor of TGF‐β receptor I and II, suppressed periodontal tissue regeneration in immunodeficient mice. In the beagle dog with Class II furcation defects, PDLSC‐CP regenerated and repaired periodontal bone defects, which is more effective than the control group, the bone substitutes group, and the mixed group (PDLSC‐CP and bone substitutes). These findings highlight PDLSC‐CP as a promising strategy for periodontal bone defect treatment, where autocrine TGF‐β1 stimulates the TGF‐β1/Smad pathway to drive periodontal tissue regeneration.

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.

100 项与 LY-2109761 相关的药物交易

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