CELLULAR SIGNALLING
·
2024
·
IF 4.4
Jingwen Shi,Wenda Jing,Yueyun He,Ying Huang
Despite decades of research, endometriosis remains a mysterious gynecological disease with unknown etiology and pathogenesis. Krüppel-like Factor 6 (KLF6), a transcription factor, has a wide expression profile and regulates a variety of biological processes. Here, we investigated the expression and function of KLF6 and its possible regulatory mechanisms in endometriosis. To determine the function of KLF6, knockdown and overexpression experiments were performed in eutopic endometrial stromal cells (EU-ESCs) and ectopic endometrial stromal cells (EC-ESCs), respectively. Cell viability, apoptosis, migration, invasion, and angiogenesis assays were conducted in ESCs. ChIP-sequencing and mRNA-sequencing were performed to investigate the functional mechanism of KLF6 in regulating ESCs. We found that KLF6 was highly expressed in eutopic endometrium of endometriosis patients, compared with ectopic endometrium. Similarly, the same was true in EU-ESCs, which was compared with EC-ESCs. Overexpression of KLF6 significantly suppressed EC-ESC proliferation, migration and invasion and induced cell apoptosis, while knockdown of KLF6 resulted in the opposite effects on EU-ESCs. Overexpression of KLF6 significantly inhibited EC-ESC angiogenesis. Mechanistically, the results of ChIP sequencing and mRNA sequencing revealed that CTNNB1 may be a transcriptional target regulated by KLF6. Reintroduction of KLF6 reversed the effects of KLF6 knockdown on EU-ESCs. KLF6 inhibited the proliferation, migration and angiogenesis of EC-ESCs by inhibiting the expression of CTNNB1. Our findings provided a new perspective on the role of KLF6 in endometriosis progression and inspire potential targeted therapeutic strategies.
研究领域:
妇科学
·
分子生物学
·
转录因子
·
疾病发病机制
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PEDIATRIC RESEARCH
·
2023
·
IF 3.6
Wang Qi,Shi Xulai,Li Ping-Ping,Gao Li,Zhou Yueyuan,Li Luyao,Ye Hao,Fu Xiaoqin,Li Peijun
Background Although previous studies show that microRNAs (miRNAs) can potentially be used as diagnostic markers for epilepsy, there are very few analyses of pediatric epilepsy patients. Methods miRNA profiles using miRNA-seq was performed on plasma samples from 14 pediatric epileptic patients and 14 healthy children. miRNA miR-27a-3p that were significantly changed between two groups were further evaluated. The potential target genes of miR-27a-3p were screened through unbiased mRNA-seq and further validated using Western blot and immunohistochemistry in HEK-293T cells and in the brains of mice with epilepsy induced by lithium chloride–pilocarpine. Results We found 82 upregulated and 76 downregulated miRNAs in the plasma from pediatric patients compared with controls ( p < 0.01), of which miR-27a-3p exhibited a very low p value ( p < 0.0001) and validated in additional plasma samples. Two genes, GOLM1 and LIMK1, whose mRNA levels were decreased ( p < 0.001) with the increase of miR-27a-3p were further validated in both HEK-293T cells and in epileptic mice. Conclusions MiR-27a-3p exhibits potential as a diagnostic and therapeutic marker for epilepsy. We postulate that additional studies on the downstream targets of miR-27a-3p will unravel its roles in epileptogenesis or disease progression. Impact
A total of 158 differentially expressed miRNAs were detected in plasma between epileptic and control children.
Plasma miR-27a-3p was one of the miRNAs with a low p value.
GOLM1 and LIMK1 were validated as downstream target genes of miR-27a-3p.
miR-27a-3p has potential as a diagnostic and therapeutic marker for epilepsy.
研究领域:
神经科学
·
分子生物学
·
儿科
·
生物标志物研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2023
·
IF 8.4
Wenyi Wang,Junli Chang,Hongfeng Ruan,Xingyuan Sun,Fulai Zhao,Peng Zhao,Chujie Zhou,Junjie Tong,Suxia Guo,Qi Shi,Yongjun Wang,Weian Zhang,Yanping Yang
Cancer is a global leading cause of death, with nearly 10 million people dying from cancer in 2020. Photodynamic therapy (PDT) has emerged as a promising cancer treatment modality; however, the potential molecular mechanisms remain obscure. Herein, we designed a near-infrared (NIR) light-activated nanoplatform (TPBC-PEG) to explore the therapeutic effects and mechanisms of PDT by using a model of intratibial primary and pulmonary metastasis osteosarcoma. Under laser irradiation, TPBC-PEG photosensitizer dose-dependently inhibited proliferative and metastatic capabilities while promoting apoptosis of osteosarcoma cells in vitro, and also effectively suppressed carcinogenesis and pulmonary metastasis in osteosarcoma xenograft mouse model. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis after high-throughput mRNA-seq indicated that the HIPPO signaling pathway was one of the 20 most significantly related signaling pathways. And a series of experiments for determining the HIPPO signaling activity were conducted to reconfirm the specificity. Collectively, PDT of TPBC-PEG micelles against carcinogenesis and pulmonary metastasis of deep-seated intratibial osteosarcoma was achieved by activating HIPPO signaling pathway. Our study identified a hitherto uncharacterized molecular mechanism of PDT, which may provide new insights to understand and design promising nanoplatforms for future cancer therapies.
研究领域:
肿瘤学
·
分子生物学
·
治疗学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
CELLULAR & MOLECULAR BIOLOGY LETTERS
·
2023
·Vol. 28
·期 1
·1-24
·
IF 8.3
Lei Ming,Lin Hui,Shi Deyao,Hong Pan,Song Hui,Herman Bomansaan,Liao Zhiwei,Yang Cao
Background Intervertebral disc degeneration (IVDD) is the major cause of low-back pain. Histone deacetylase 9 (HDAC9) was dramatically decreased in the degenerative nucleus pulposus (NP) samples of patients with intervertebral disc degeneration (IVDD) according to bioinformatics analysis of Gene Expression Omnibus (GEO) GSE56081 dataset. This study aims to investigate the role of HDAC9 in IVDD progression.Methods The contribution of HDAC9 to the progression of IVDD was assessed using HDAC9 knockout (HDAC9KO) mice and NP-targeted HDAC9-overexpressing mice by IVD injection of adenovirus-mediated HDAC9 under a Col2a1 promoter. Magnetic resonance imaging (MRI) and histological analysis were used to examine the degeneration of IVD. NP cells were isolated from mice to investigate the effects of HDAC9 on apoptosis and viability. mRNA-seq and coimmunoprecipitation/mass spectrometry (co-IP/MS) analysis were used to analyze the HDAC9-regulated factors in the primary cultured NP cells.Results HDAC9 was statistically decreased in the NP tissues in aged mice. HDAC9KO mice spontaneously developed age-related IVDD compared with wild-type (HDAC9WT) mice. In addition, overexpression of HDAC9 in NP cells alleviated IVDD symptoms in a surgically-induced IVDD mouse model. In an in vitro assay, knockdown of HDAC9 inhibited cell viability and promoted cell apoptosis of NP cells, and HDAC9 overexpression had the opposite effects in NP cells isolated from HDAC9KO mice. Results of mRNA-seq and co-IP/MS analysis revealed the possible proteins and signaling pathways regulated by HDAC9 in NP cells. RUNX family transcription factor 3 (RUNX3) was screened out for further study, and RUNX3 was found to be deacetylated and stabilized by HDAC9. Knockdown of RUNX3 restored the effects of HDAC9 silencing on NP cells by inhibiting apoptosis and increasing viability.Conclusion Our results suggest that HDAC9 plays an important role in the development and progression of IVDD. It might be required to protect NP cells against the loss of cell viability and apoptosis by inhibiting RUNX3 acetylation and expression during IVDD. Together, our findings suggest that HDAC9 may be a potential therapeutic target in IVDD.Graphical Abstract
研究领域:
骨科
·
分子生物学
·
治疗学
·
生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PULMONARY PHARMACOLOGY & THERAPEUTICS
·
2024
·
IF 3.3
Huijuan Zhang,Jianli Qiu,Qianyi Zhao,Yong Zhang,Haitao Zheng,Ziying Dou,Yongbin Yan
Pulmonary fibrosis is a complex disease that can occur in a variety of clinical settings. The Zinc Finger and BTB Domain Containing 16 (Zbtb16) is a transcription factor and has not been studied in pulmonary fibrosis. Lung tissues from rats which were treated with bleomycin and Tanshinone IIA (Tan IIA) were collected for mRNA sequencing. Zbtb16, a differentially expressed gene, was screened. Using adeno-associated virus to knock down Zbtb16 in rats, it was found that the lung index and the content of hydroxyproline in lung tissue were decreased. HE and Masson staining revealed that pathological symptoms of lung histopathology were relieved after Zbtb16 knockdown. Protein expressions of α-SMA, Collagen I and Fibronectin were significantly decreased after Zbtb16 knockdown in vivo and in vitro . Meanwhile, the protein content of TGF-β1 and the phosphorylation of Smad2/3 were inhibited by Zbtb16 knockdown. Conversely, under the treatment of Tan IIA and TGF-β1, overexpression of Zbtb16 improved cell viability, increased the expression of fibrosis-related proteins, and promoted the phosphorylation of Smad 2/3. All above demonstrates that Zbtb16 inhibition ameliorates pulmonary fibrosis and suppresses the TGF-β/Smad pathway. Furthermore, Zbtb16 mediates the inhibitory process of Tan IIA on pulmonary fibrosis. This study provides a novel candidate therapeutic target for pulmonary fibrosis.
研究领域:
药理学
·
肺病学
·
分子生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 8
·1725-1738
·
IF 7
Xin Sun,Xin Jiao,Zengguang Wang,Jie Ma,Tianchang Wang,Dan Zhu,Han Li,Liang Tang,Heyue Li,Changde Wang,Yiming Li,Chen Xu,Jinwu Wang,Yaogai Gan,Wenjie Jin
Cellular bioactivity and tissue regeneration can be affected by coatings on tissue-engineered scaffolds. Using mussel-inspired polydopamine (PDA) is a convenient and effective approach to surface modification. Therefore, 3D-printed β-tricalcium phosphate (β-TCP) scaffolds were coated with PDA in this study. The effects of the scaffolds on the adhesion and osteogenic differentiation of seeded bone marrow mesenchymal stem cells (BMSCs) in vitro and on new-bone formation in vivo were investigated. The potential mechanisms and related differential genes were assessed using mRNA sequencing. It was seen that PDA coating increased the surface roughness of the 3D-printed β-TCP scaffolds. Furthermore, it prompted the adhesion and osteogenic differentiation of seeded BMSCs. mRNA sequencing analysis revealed that PDA coating might affect the osteogenic differentiation of BMSCs through the calcium signaling pathway, Wnt signaling pathway, TGF-beta signaling pathway, etc. Moreover, the expression of osteogenesis-related genes, such as R-spondin 1 and chemokine c-c-motif ligand 2, was increased. Finally, both the 3D-printed β-TCP scaffolds and PDA-coated scaffolds could significantly accelerate the formation of new bone in critical-size calvarial defects in rats compared with the control group; and the new bone formation was obviously higher in the PDA-coated scaffolds than in β-TCP scaffolds. In summary, 3D-printed β-TCP scaffolds with a PDA coating can improve the physicochemical characteristics and cellular bioactivity of the scaffold surface for bone regeneration. Potential differential genes were identified, which can be used as a foundation for further research.
研究领域:
生物材料
·
组织工程
·
干细胞生物学
·
分子生物学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）