CELL BIOLOGY AND TOXICOLOGY
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2025
·Vol. 41
·期 1
·1-29
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IF 5.9
Tian Sirui,Yu Haiyang,Yang Ruoxuan,Wang Heshi,Zhao Baohong,Wang Danning
Soft tissue injury (STI) is a prevalent condition that requires effective therapeutic approaches. The focus of this investigation was to elucidate the molecular mechanisms linked to the IGFBP3 protein in adipose-derived stem cells (ADSCs) for STI repair, utilizing single-cell multiomics technology and a 3D bioprinting model. Establishment of a mouse-based STI model facilitated the comparison of cellular compositions and communication variances between wounded and normal tissues through single-cell RNA sequencing (scRNA-seq). High-throughput transcriptomics and bioinformatics analysis pinpointed IGFBP3 as a key target in ADSCs related to STI repair. In vitro experiments assessed IGFBP3's effects on ADSCs' epithelial cell differentiation, proliferation, and migration using various assays and lentivirus transfection to manipulate IGFBP3 expression. A 3D bioprinting technique was used to create an ADSCs-IGFBP3 peptide self-assembling hydrogel scaffold, characterized by Fourier-transform infrared spectroscopy, X-ray diffraction, SEM, and TEM. The scaffold's efficacy was validated in an animal model. Results showed nine cell subtypes in both normal and injured tissues, with increased ADSCs in STI tissues exhibiting enhanced connectivity and interactions. RNA-seq analysis confirmed IGFBP3 as crucial for ADSCs and STI. In vitro and 3D bioprinting experiments, along with animal model validation, confirmed IGFBP3's role in STI repair. Upregulation of IGFBP3 in ADSCs promoted epithelial cell differentiation by enhancing ITGB1 expression, activating the ERK pathway to boost cell proliferation and migration. This study highlights IGFBP3's significant role in ADSCs for STI repair, providing potential molecular targets for developing new treatments. The findings offer valuable insights into IGFBP3's mechanisms, aiding in advancing STI therapeutic strategies. Graphical 1. IGFBP3 enhances ADSC function in STI repair by activating ITGB1 and ERK pathways. 2. High IGFBP3 expression promotes ADSC differentiation into epithelial cells, improving tissue regeneration. 3. Single-cell multiomics and 3D bioprinting validate IGFBP3’s role in advancing STI treatment. 4. Findings present IGFBP3 as a promising molecular target for clinical STI therapy.
研究领域:
再生医学
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分子生物学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
International Journal of Biological Sciences
·
2021
·
IF 6.582
Yadong Liu,Huiyan Lv,Xingyi Li,Jiannan Liu,Song Chen,Yaodong Chen,Yinshan Jin,Ruihua An,Shiliang Yu,Zhigang Wang
Of all pathological types of renal cell cancer (RCC), clear cell renal cell carcinoma (ccRCC) has the highest incidence. Cyclovirobuxine (CVB), a triterpenoid alkaloid isolated from Buxus microphylla , exhibits antitumour activity against gastric cancer and breast cancer; however, the mechanism by which CVB inhibits ccRCC remains unclear. The aim of our study was to explore the antitumour effects of CVB on ccRCC and to elucidate its exact mechanism. Cell viability, proliferation, cell cycle distribution, apoptosis, wound healing and invasion were evaluated. Furthermore, Western blotting, immunofluorescence staining, immunohistochemical staining, and bioinformatics analyses were utilized to comprehensively probe the molecular mechanisms. The in vivo curative effect of CVB was explored using a 786-O xenograft model established in nude mice. CVB reduced cell viability, proliferation, angiogenesis, the epithelial-mesenchymal transition (EMT), migration and invasion. In addition, CVB induced cell cycle arrest in S phase and promoted apoptosis. The expression of the EMT-related transcription factor Snail was significantly downregulated by CVB via the inhibition of the AKT, STAT3 and MAPK pathways. We revealed that insulin-like growth factor binding protein 3 (IGFBP3) was the true therapeutic target of CVB. CVB exerted anti-ccRCC effects by blocking the IGFBP3-AKT/STAT3/MAPK-Snail pathway. Targeted inhibition of IGFBP3 with CVB treatment may become a promising therapeutic regimen for ccRCC.
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICAL RESEARCH
·
2025
·Vol. 30
·期 1
·1-13
·
IF 3.4
Luo Liling,Jiang Chao,Xie Songxi
Background Previous studies showed that high mobility group box-1 (HMGB1) facilitates the initiation and progression of esophageal squamous cell carcinoma (ESCC), and the current research investigated the detailed mechanisms implicated.Methods The impact of HMGB1 and IGFBP3 levels on the survival of ESCC was examined by plotting Kaplan–Meier (KM) curves based on the data collected from The Cancer Genome Atlas (TCGA). Quantitative real-time PCR (qRT-PCR) was performed to detect the expressions of HMGB1 in both human esophageal epithelial cells (HEEC) and ESCC cells. After cell transfection, the proliferation of ESCC cells was measured, and the cell metastasis was determined based on the levels of cadherins (CDHs) and Vimentin (VIM). Macrophage polarization was determined by calculating the mean fluorescence intensity (MFI) of CD206 and CD86. In addition, co-immunoprecipitation and immunoblotting were applied to evaluate the interaction between insulin-like growth factor binding protein 3 (IGFBP3)/DNA-dependent protein kinase catalytic subunit (DNA–PKcs) and HMGB1.Results A high level of HMGB1 was predictive of an unfavorable prognosis of ESCC (p < 0.05). HMGB1 showed a higher expression in ESCC cells (p < 0.05), while knockdown of HMGB1 inhibited ESCC cell proliferation, downregulated the levels of CDH2 and VIM and upregulated the level of CDH1 (p < 0.05). In contrast, overexpressed HMGB1 showed the opposite effects (p < 0.05), suggesting the role of HMGB1 in the epithelial–mesenchymal transition (EMT) of ESCC. After the knockout of HMGB1, the MFI of CD86 was increased but that of CD206 was reduced, indicating the polarization towards M1 macrophages (p < 0.05). However, the results were reversed when HMGB1 was overexpressed (p < 0.05). Meanwhile, HMGB1 could interact with the IGFBP3/DNA–PKcs complex (p < 0.05). Low-expressed IGFBP3 was predictive of an unfavorable prognosis of ESCC, and IGFBP3 silencing promoted the proliferation of ESCC cells (p < 0.05). Besides, HMGB1 and IGFBP3 could act antagonistically in influencing the proliferation of ESCC cells and macrophage polarization.Conclusion sThrough in vitro experiments, this study found that HMGB1 was linked to the proliferation and polarization of macrophages in ESCC, providing novel evidence for the role of HMGB1 in ESCC development.
研究领域:
肿瘤学
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分子生物学
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免疫学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
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