Molecular Medicine Reports
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2016
·Vol. 13
·期 4
·3567-3573
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IF 1.559
Ke Jiang,Guo Chun,Ziming Wang,Quanyin Du,Aimin Wang,Yan Xiong
Tendon adhesion is a common problem in the healing of injured tendons. The molecular mechanisms of the TGF-β/Smad signaling pathway have been determined, and the role of TGF-β has been well characterized in wound healing. However, the intracellular mechanism or downstream signals by which TGF-β3 modulates its effects on tendon healing have not been well elucidated. The aim of this study was to determine the effect of TGF‑β3 on the TGF-β/Smad signaling pathway in tenocytes. Quantitative polymerase chain reaction and western blot analysis were used to analyze the effect of TGF‑β3 on the regulation of the expression of Smad proteins in tenocytes. The results demonstrated that TGF‑β3 has no significant effect on the proliferation of tendon cells. The addition of TGF‑β3 to tenocytes can significantly downregulate the expression of Smad3 and upregulate the expression of Smad7 at the gene and protein levels. The results demonstrate that TGF‑β3 may regulate Smad3 and Smad7 proteins through the TGF-β/Smad signaling pathway to minimize extrinsic scarring. Thus, it may provide a novel approach to decrease tendon adhesion and promote tendon healing.
研究领域:
分子生物学
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细胞生物学
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骨科
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DOI
PubMed
高影响因子
American Journal of Translational Research
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2017
·
IF 2.829
Chong Zhong,Yong-Fa Zhang,Jun-Hai Huang,Zi-Yu Wang,Qiu-Yuan Chen,Li-Tian Su,Zhen-Tao Liu,Cheng-Ming Xiong,Zhi Tao,Rong-Ping Guo
Background: Hepatocellular carcinoma (HCC) is one of the most common and aggressive malignant tumors in the world. In China, traditional medicine is commonly used in the treatment of cancer. Among these medicines, Jianpi Huayu Decoction (JHD) is a typical clinical prescription against multiple tumors. However, the exact function and targets of JHD are currently unknown. The aim of this study is to assess the efficacy of JHD against HCC. Methods and results: Hepatic carcinoma SMMC7221 cells were treated with JHD drug-serum in a dose- and time-dependent manner. Real-time PCR (RT-PCR), western-blot (WB), and immunofluorescence microscopy revealed that JHD increased both the mRNA and protein levels of Smad7 and decreased the protein level of p-Smad3. It subsequently increased the E-cadherin expression level and decreased those of N-cadherin and Vimentin. Metastasis and invasion were eventually inhibited, as determined by the wound healing and transwell invasion assays. Treatment of Tanshinone IIA (Tan IIA) showed similar results as JHD, indicating that it is most likely the main functional drug monomer of JHD. The in vivo assay in nude mice also revealed the efficacy of JHD to inhibit epithelial mesenchymal transition (EMT). Conclusion: JHD was shown to be an effective therapeutic strategy against HCC.
研究领域:
肿瘤学
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分子生物学
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中医药学
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DOI
PubMed
高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
·
2024
·
IF 4.8
Qing Zheng,Feng-Ping Lei,Shan Hui,Ming Tong,Li-Hui Liang
Cellular senescence is an adverse factor in the development of pulmonary fibrosis (PF). Ginsenoside Rb1 has been found to inhibit both cellular senescence and PF. This study aimed to elucidate the molecular mechanisms by which ginsenoside Rb1 regulates cellular senescence and PF. A PF mouse model was established by Bleomycin (BLM) administration, and a cell model of senescence was constructed using MRC-5 cells treated with Adriamycin RD (ARD) administration. Hematoxylin and Eosin (HE) staining and Masson staining were employed to evaluate cellular structure and collagen fiber content. RT-qPCR and western blotting were used to detect mRNA and protein expression of the target genes. Enzyme-linked Immunosorbent Assay (ELISA) was applied to measure the protein concentration of IL-1 β and IL-18. SA- β -gal staining was used to evaluate cellular senescence. Our results show that ginsenoside Rb1 effectively suppressed BLM-induced PF in mice. ARD administration to induce cellular senescence reduced NRF2, QKI, and SMAD7 expression in MRC-5 cells. By inducing NRF2 overexpression, ARD-induced cellular senescence and fibrosis in MRC-5 cells were relieved. Notably, NRF2 knockdown abolished the mitigating effects of ginsenoside Rb1 on ARD-induced cellular senescence and fibrosis in MRC-5 cells. Mechanistically, NRF2 increased SMAD7 mRNA stability through the transcriptional regulation of QKI. As expected, ginsenoside Rb1 alleviated ARD-induced senescence and fibrosis in MRC-5 cells by activating the NRF2/QKI/SMAD7 axis. Therefore, it was found that ginsenoside Rb1 mitigates cellular senescence and fibrosis during PF progression by activating the NRF2/QKI/SMAD7 axis. This study provides a potential therapeutic strategy for the treatment of PF and elucidates its mechanism of action.
研究领域:
药理学
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呼吸病学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
BMC Cardiovascular Disorders
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2024
·Vol. 24
·期 1
·1-11
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IF 2
Lin Wei,Hou Lianglei,Tang Jialyu,Huang Anwu,Jia Zhuyin
In this study, we sought to investigate the mechanisms of action of miR-195-5p in the osteogenic differentiation of vascular smooth muscle cells (VSMCs), and thereby provide novel insights and a reference for the targeted therapy of arterial media calcification. VSMC differentiation was induced using sodium β-glycerophosphate, and we investigated the effects of transfecting cells with miR-195-5p mimics, vectors overexpressing Smad7, and the Wnt/β-catenin pathway inhibitor (KYA1797K) on VSMC differentiation by determining cell viability and apoptosis, and the mRNA and protein expression of factors associated with osteogenic differentiation and the Wnt/β-catenin pathway. The results revealed that miR-195-5p mimics enhanced the osteogenic differentiation of VSMCs induced by β-glycerophosphate, whereas the overexpression of Smad7 reversed this phenomenon. In addition, KYA1797K was found to promote the effects of Smad7 overexpression. In conclusion, by targeting, Smad7, miR-195-5p promotes the Wnt/β-catenin pathway. and thus the osteogenic differentiation of VSMCs. These findings will provide a reference for elucidating the mechanisms whereby miR-195-5p regulates osteogenic differentiation.
研究领域:
分子生物学
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细胞生物学
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心血管研究
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DOI
PubMed
高影响因子
HUMAN & EXPERIMENTAL TOXICOLOGY
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2020
·Vol. 40
·期 4
·587-595
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IF 2.067
H-J Wang,H Liu,Y-H Lin,S-J Zhang
Diabetic nephropathy (DN) is primary cause of end-stage renal disease. A previous study has shown that miR-32-5p (miR-32) is highly expressed in kidney tissue during chronic allograft dysfunction with interstitial fibrosis and tubular atrophy. However, the role of miR-32-5p (miR-32) in DN is still unclear. In this study, streptozotocin-induced DN rat models and high glucose (HG)-incubated human kidney proximal tubular epithelial (HK-2) cells were established to investigate the role and underlying mechanisms of miR-32 in DN. Results of real-time PCR revealed that miR-32 levels were greatly increased in DN rats and HG-incubated HK-2 cells. Downregulation of miR-32 effectively relieved HG-induced autophagy suppression, fibrosis, epithelial-mesenchymal transition (EMT) and inflammation in HK-2 cells. Besides, miR-32 overexpression significantly down-regulated the expression of mothers against decapentaplegic homolog 7 (SMAD7), whereas knockdown of miR-32 markedly up-regulated the level of SMAD7. Dual-luciferase reporter gene assay confirmed that SMAD7 was a target of miR-32. Reintroduction of SMAD7 expression rescued miR-32-induced HK-2 cells autophagy suppression, EMT and renal fibrosis. Our findings indicate that miR-32 may play roles in the progression of EMT and fibrosis in DN.
研究领域:
分子生物学
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肾病学
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糖尿病研究
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DOI
PubMed
高影响因子
EXPERIMENTAL EYE RESEARCH
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2025
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IF 2.7
Yarong Yan,Shulei Xing,Jinghua Liu,Xinlin Yan,Yi Guan,Zhixin Jiang,Wei Zhang,Xuan Li
Lycium barbarum glycopeptide (LbGp), derived from the Chinese medicinal plant Lycium barbarum, has demonstrated anti-inflammatory properties; however, its precise role and mechanism in corneal repair following injury remain elusive. The present research investigated the mechanisms and effects of LbGp on corneal repair following alkali burn injury using in vivo mouse models of corneal alkali burn and in vitro human keratocyte fibrosis models. Corneal inflammation, opacity, and epithelial defects were assessed via a slit lamp microscope. Results showed that LbGp-treated mice exhibited reduced edema, accelerated re-epithelialization, and decreased corneal opacity compared to the phosphate-buffered saline (PBS)-treated controls. Proteomic analysis revealed altered proteins enriched in the extracellular matrix among the control, injury, and LbGp treatment groups. Moreover, LbGp significantly attenuated TGFβ-1-induced myofibroblasts transdifferentiation from keratocytes. Consistently, LbGp treatment inhibited the upregulation of fibrosis markers (αSMA, fibronectin, and collagen III) at both the protein and mRNA levels after corneal alkali burns. LbGp also effectively suppressed the activation of the NF-κB/NLRP3/IL-1β signaling pathway and neutrophil infiltration following corneal alkali burn injury. Additionally, miR-21 was upregulated in TGFβ-1-stimulated keratocytes and in the alkali-burned mouse cornea. LbGp decreased miR-21 expression, while increasing expression of its target, Smad7, thereby dampening the TGFβ/Smad2/3 signaling pathway. This research demonstrates that LbGp promotes corneal healing by inhibiting inflammation and fibrosis after alkali burns, suggesting its potential as a supplementary therapy for corneal injury repair.
研究领域:
药理学
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眼科
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Ye Liu,Jiufeng Zhao,Xingrui Mu,Junyu Deng,Xingqian Wu,Wenjie He,Yiqiu Liu,Rifang Gu,Felicity Han,Xuqiang Nie
Ethnopharmacological relevance Centella asiatica (L.) Urban is an ethnobotanical herb. The main bioactive components of Centella asiatica are pentacyclic triterpenoid glycosides , namely asiaticoside and hydroxyasiaticoside. Asiaticoside possess a diverse array of pharmacological properties, such as wound-healing, anti-inflammatory, antioxidant, anti-allergic, antidepressant, anxiolytic, anti-fibrotic, antibacterial, anti-arthritic, anti-tumor, and immunomodulatory activities. Aim of the study The purpose of this investigation is to explore potential therapeutic interventions for the delayed healing of wounds in diabetic patients (DW) facilitated by Asiaticoside-Nitric Oxide. To clarify the key molecular mechanism of miRNA-21-5p in DW wound repair and to deepen the understanding of DW disease pathogenesis. Materials and methods Firstly, miRNA microarray technology, bioinformatics, and RT-qPCR were used to analyze DW patients' and normal controls' skin tissue samples. Secondly, in order to investigate the role of miRNA-21-5p, a hyperglycemic model was established using HaCaT cells. Overexpressing as well as interfering HaCaT cell lines were constructed by lentiviral infection to further explore the proliferative and migratory effects of Asiaticoside-Nitric Oxide. The next step was to search for potential target genes of miRNA-21-5p and verify them with dual-luciferase reporter assay. Finally, the expression levels of target genes and proteins were detected through the utilization of RT-qPCR and Western blotting under the influence of Asiaticoside-Nitric Oxide. Results A library of miRNAs and target genes expressed explicitly in DW patients and rats was established. The study confirmed the upregulation of miRNA-21-5p in DW patients and identified its involvement in signaling pathways related to chronic ulcer wound repair. Overexpression of LV-miRNA-21-5p significantly promoted cell proliferation , while treatments of Asiaticoside-Low dose (AC-L) and Asiaticoside-Medium dose (AC-M) enhanced proliferation and migration, particularly when combined with nitroprusside (SNP). Further analysis revealed potential target genes of miRNA-21-5p, such as TGF-β1, SMAD7, and TIMP3. Their interaction with miRNA-21-5p was confirmed through dual luciferase assays. The study found that anti-DW drugs increased the expression of TGF-β1 and SMAD7 while inhibiting TIMP3 expression in a high-glucose environment. Conclusions The research concluded that miRNA-21-5p plays a crucial role in the delayed healing of diabetic wounds, and that the combination treatment of AC + SNP shows promise in promoting wound healing in DW rats. Target genes, including TGF-β1, SMAD7, and TIMP3, may contribute to the regulatory mechanisms involved in diabetic wound healing. These findings provide valuable insights for developing novel therapeutic approaches for DW.
研究领域:
药理学
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分子生物学
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糖尿病研究
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伤口愈合
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民族药理学
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DOI
PubMed
高影响因子
Bioengineered
·
2022
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IF 6.832
Ning Han,Fei Qian,Xianping Niu,Guoting Chen
Osteonecrosis of the femoral head (ONFH) caused by steroids is a severe orthopedic disorder resulting from the use of high-dose steroid drugs, characterized by structural changes in the bone, joint dysfunction, and femoral head collapse. CircRNAs and miRNAs have increasingly been suggested to play pivotal roles in osteogenic differentiation and osteogenesis. Significant upregulation of circ_0058792 was observed in patients with steroid-induced ONFH. Bioinformatic analysis showed that circ_0058792 might act as a sponge for miR-181a-5p. This study further investigated the mechanisms underlying the role of circ_0058792 and miR-181a-5p in osteogenic differentiation in methylprednisolone-induced ONFH rats and MC3T3-E1 cells. The results showed a notable decrease in the serum of miR-181a-5p in methylprednisolone-induced ONFH rats. Silencing of circ_0058792 using siRNAs and overexpression of miR-181a-5p significantly increased alkaline phosphatase activity and matrix mineralization capacity. Additionally, markers for osteogenic differentiation were significantly upregulated in miR-181a-5p-transfected cells. However, overexpression of circ_0058792 and the addition of the miR-181a-5p inhibitor reversed this increase. Smad7 was identified to be miR-181a-5p’s direct target and circ_0058792 was confirmed to be miR-181a-5p’s competing endogenous RNA (ceRNA). Upregulation of miR-181a-5p promotes phosphorylation of Smad2 and Smad3. Furthermore, circ_0058792 and miR-181a-5p had opposing effects on Smad7 expression. Collectively, these findings indicate that circ_0058792 regulates osteogenic differentiation by sponging miR-181a-5p via the TGF-β/Smad7 pathway. These findings elucidated the functions of circ_0058792 and miR-181a-5p in the regulation of steroid-induced ONFH. Our findings also indicated that circ_0058792 and miR-181a-5p are possible diagnostic markers and therapeutic targets for treating steroid-induced ONFH.
研究领域:
骨科
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分子生物学
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遗传学
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DOI
PubMed
高影响因子
BIOTECHNIC & HISTOCHEMISTRY
·
2026
·
IF 1.4
Ying Xun,Xiaoli Wang,Lili Chen,Yu Fu,Xiang Wu,Wenqing Zeng
Glucose-lowering treatment and antidiabetic drugs show great potential for preventing and intervening in diabetes mellitus (DM)-associated cognitive dysfunction or advanced dementia. This study delves into the role and mechanism of low-carbohydrate diet (LCD) combined with Xiaokeping (XKP) on these conditions. Type 2 diabetes (T2D) rat models were constructed via high-fat diet and streptozotocin (STZ) injection, and treated with LCD and XKP alone or in combination for 8 weeks. Body weight and indicators of blood glucose and lipids were determined. Additionally, memory and spatial learning abilities were assessed. Tissue staining of the hippocampus was used to observe pathological changes. Oxidative stress, levels of inflammatory factors, and phosphatidylinositol 3-kinase (PI3K)/Akt serine/threonine kinase (Akt) were analyzed. The results demonstrated that LCD and/or XKP treatment recovered body weight, blood glucose, and lipid balance, while enhancing spatial memory and attenuating lesion in the hippocampus of diabetic rats. LCD and/or XKP treatment increased superoxide dismutase, decreased malondialdehyde, interleukin-1β/6, and tumor necrosis factor alpha level in the hippocampus of diabetic rats, which suggests a reduction in oxidative stress and neuroinflammation. Moreover, LCD and/or XKP treatment activated the PI3K/Akt pathway. LCD combined with XKP displayed superior efficacy compared to monotherapy. Collectively, LCD combined with XKP mixture improves cognitive decline of T2D rats by suppressing oxidative stress and neuroinflammation in the hippocampus, through a mechanism involving the activation of the PI3K/Akt pathway.
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DOI
PubMed
高影响因子
Chinese Herbal Medicines
·
2023
·
IF 3.8
Yanshan Zhan,Xiaoqi Xu,Xi Luo,Ruiping Liu,Yujian Lin,Ping Zhao,Jun Shi
Objective Hypertrophic scars (HS) are a variety of skin tissue fibrosis disease that occurs in human skin, the effective therapeutic method of which is still inaccessible up to now. As a bioactive constituent of a well-known medical plant, Salvia miltiorrhiza (Danshen in Chinese), tanshinone II A (TSA) is reported to inhibit cell proliferation in HS. Therefore, the aim of this study was to prepare TSA self-soluble microneedles to strengthen its dermal retention and break through the difficulty of significantly thickening epidermal connective tissue and stratum corneum at the HS site. The possible mechanism of action in suppressing HS was studied using human skin fibroblasts (HSF). Methods Tanshinone II A self-dissolving microneedles (TSA-MN) was prepared using a negative mold casting method. The prescription process of microneedle was optimized by Box-Behnken effect surface method. Different media were selected to investigate the ability of transdermal absorption and in vitro release. Furthermore, according to Cell Counting Kit-8 (CCK8) method as well as the Western blot method, the effect of TSA-MN on the biological characteristics of HSF was investigated. Results With remarkable slow release effect and dermal retention, the release and transdermal properties of TSA-MN in vitro were better than both TSA and ordinary dosage forms. Its effect of HSF confirmed the essential decrease in cell motility during cell proliferation and cell migration in vitro , which plays a significant role in down-regulating the secretion of transforming growth factor- β 1 (TGF- β 1 ) in HSF and increasing the expression level of Smad7. Conclusion The prepared TSA self-soluble microneedles is helpful in solving the problem of hypertrophic scars, with a stable dermal retention effect after process optimization.
研究领域:
药学
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皮肤病学
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生物技术
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Biomaterials and Tissue Engineering
·
2020
·Vol. 10
·期 6
·812-822
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IF 0.511
Bai Yi-Hua,Yang Min,Wang Jia-Ping,Jiang Hong-Ying,Li Luo-Hua,Zhang Xin-Xin,Ma Li
The present study aims to probe the impact of mesenchymal stem cells (MSCs) on the HMGA2 gene and renal tubular epithelial cell EMT in diabetic nephropathy (DN). The advanced glycation end product (AGE) in the later period was used to interfere with the HK-2 cell modeling of humans
in vitro, while STZ was used for the modeling of mice DN in vivo. Allogeneic MSCs were used to interfere with the model to detect the concentration of the correlation factor in cells and mice kidney tissues and HMGA2 expression level. The following aspects were prompted after
treatment with MSCs in vitro and in vivo: (1) TGF-β1 concentration, Smad2, HMGA2, vimentin and α-SMA expression levels were significantly reduced, when compared to the model group (P <0.05), while Smad7 and E-cadherin expression levels significantly
increased, when compared to the model group (P <0.05); (2) The proteinuria and serum creatinine level of mice were alleviated, and the ultrastructure damage condition of kidneys also improved, when compared to the model group. MSCs can restrain the high expression of HMGA2 in DN,
EMT and kidney fibrosis, and postpone renal function progression.
研究领域:
分子生物学
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干细胞研究
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肾病学
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糖尿病学
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DOI
高影响因子
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