BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2024
·
IF 4.2
Lin Lv,Keying Yuan,Jiahao Li,Jing Lu,Qi Zhao,Hongyan Wang,Qiuyu Chen,Xinyu Dong,Siqi Sheng,Mingyu Liu,Yuanqi Shi,Hongquan Jiang,Zengxiang Dong
Myocardial fibroblasts transform into myofibroblasts during the progression of cardiac fibrosis, together with excessive cardiac fibroblast proliferation. Hence, the prevention and treatment of cardiac fibrosis are significant factors for inhibiting the development of heart failure. P-element Induced WImpy testis-interacting RNAs (PiRNA) are widely expressed in the heart, but their involvement in cardiac fibrosis has not yet been confirmed. We identified differentially expressed PiRNAs using Arraystar PiRNA expression profiling in Angiotensin II models of cardiac fibrosis in vivo and in vitro. We then explored cardiac-fibrosis-associated PiRNA-related proteins, RNA-protein interactomes, immunoprecipitation, and pulldown. We detected fibrosis markers and pathway-related proteins using immunofluorescence, qRT-PCR, and Western blot. We uncovered cardiac fibrosis associated PiRNA (CFAPIR) that was obviously dysregulated during cardiac fibrosis, whereas its overexpression reversed fibrosis in vivo and in vitro. Mechanistically, CFAPIR competitively bound muscleblind like protein 2 (MBNL2) and the cyclin-dependent kinase inhibitor P21 to regulate the TGF-β1/SMAD3 signaling pathway.
研究领域:
心脏病学
·
分子生物学
·
基因组学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2018
·
IF 3.115
Zhi-Yong Lei,Jing-Jing Chen,Zhi-Jian Cao,Ming-Zhang Ao,Long-Jiang Yu
Ethnopharmacological relevance In traditional Chinese medicine , the aerial parts of Aeschynomene indica L. (AIL) have been used for wound healing, and to treat urinary tract infection , hepatitis, enteritis , dysentery , nyctalopia , conjunctivitis, urticaria , and furuncle . However, no scientific investigation has been conducted on its wound healing potential. Aim of the study To investigate the effects of AIL extract on wound healing, isolate the active constituent and reveal the possible mechanism of enhancing wound healing. Materials and methods The circular excision wound healing model was used to evaluate in vivo wound-healing activity. Hematoxylin and eosin staining was applied to assess inflammatory cells infiltration, angiogenesis, fibroblast proliferation, collagen synthesis, collagen remodeling, and skin appendages generation. Sirius red-picric acid staining was employed for quantitative analysis of the ratio of collagen I/III. Immunohistochemical staining for CD68 , CCR7 (CD197), CD163, TGF-β1 and α-SMA was performed to determine macrophages phenotypes transition (M1-to-M2) and prove the scar-improving effect of AIL on wound healing. Results We successfully isolated the active constituent (Sub-Fr0.2) for wound healing from AIL extract, circular excision wound healing experiment and hematoxylin & eosin staining showed Sub-Fr0.2 has a significant promoting effect on wound healing. Results of sirius red-picric acid staining demonstrated a reduced ratio of collagen I/III in the Sub-Fr0.2 group as compared with the vehicle group. Immunohistochemical staining for CD68, CCR7 (CD197), and CD163 in the Sub-Fr0.2 group exhibited an elevated speed of macrophages transiting from M1 phenotype to M2 phenotype, when compared with the vehicle group. Besides, the expression of TGF-β1 and α-SMA were inhibited on wounds treated with the ointment containing Sub-Fr0.2. Conclusion Leaves of AIL and its active constituent (Sub-Fr0.2) effectively promoted wound healing and reduced scar formation, this efficacy might be exerted by accelerating macrophages phenotypes transition and inhibiting TGF-β1 and α-SMA expression.
研究领域:
药理学
·
民族药理学
·
伤口愈合
·
传统中药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2026
·
IF 3.7
Wen Qiang,Yuan Yi,Liu Zhihua,Wang Lei,Pan Chunguo
Lung cancer (LC) is a leading cause of cancer-related mortality worldwide. While the chemokine CCL25 is implicated in the tumor microenvironment, its specific role in LC is not fully understood. Here, we identify CCL25 as a key promoter of tumor progression through a novel macrophage-mediated signaling axis. Bioinformatics and clinical analyses revealed that CCL25 is highly expressed in LC and correlates with M2 macrophage infiltration and poorer patient survival. In vitro, tumor-derived CCL25 drove M2 polarization of macrophages by upregulating its receptor CCR9. Functionally, these CCL25-CCR9-induced M2 macrophages secreted TGF-β1 and significantly enhanced the proliferation, migration, and invasion of LC cells. Mechanistically, this effect was mediated through the activation of the JAK/STAT signaling pathway and the subsequent upregulation of the downstream oncogene PIM2 in tumor cells. Both pharmacological inhibition of JAK/STAT and genetic knockdown of PIM2 reversed the tumor-promoting crosstalk. Single-cell transcriptomics confirmed the presence of a TGF-β1-expressing CCR9 + M2 macrophage subset in human tumors and revealed co-expression of CCR9 and PIM2 in tumor cells. In vivo, CCL25 overexpression accelerated tumor growth and M2 macrophage infiltration. Collectively, our findings define a complete CCL25-CCR9-TGF-β1-JAK/STAT-PIM2 signaling circuit wherein tumor cells educate macrophages to, in turn, fuel their own malignant progression, highlighting this axis as a potential therapeutic target in lung cancer.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FEBS Open Bio
·
2023
·
IF 2.6
Yu Zhu,Longmei Wang,Rui Liu,Xiurong Ding,Song Yin,Yuankun Chen,Chuanlong Zhu,Zheng Wang,Wenting Li
Sepsis-induced acute kidney injury (SI-AKI) causes renal dysfunction and has a high mortality rate. Protein arginine methyltransferase-1 (PRMT1) is a key regulator of renal insufficiency. In this study, we explored the potential involvement of PRMT1 in SI-AKI. A murine model of SI-AKI was induced by cecal ligation and perforation (CLP). The expression and localization of PRMT1 and molecules involved in the TGF-β1/Smad3 and IL-6/STAT3 signaling pathways were detected in mouse kidney tissues by western blot, immunofluorescence, and immunohistochemistry. The association of PRMT1 with downstream molecules of the TGF-β1/Smad3 and IL-6/STAT3 signaling pathways were further verified in vitro in mouse renal tubular epithelial cells (mRTECs). CLP caused epithelial-mesenchymal transition (EMT), apoptosis, and inflammation in renal tissues, and this was alleviated by inhibition of PRMT1. Inhibition of PRMT1 in SI-AKI mice decreased the expression of TGF-β1 and phosphorylation of Smad3 in the renal cortex, and downregulated the expression of sIL-6R and phosphorylation of STAT3 in the medulla. Knockdown of PRMT1 in mRTECs restricted the expression of Cox-2, E-cad, Pro-caspase3 and p-Smad3 (involved in the TGF-β1-mediated signaling pathway), and blocked IL-6/sIL-6R, inducing the expression of Cox-2 and p-STAT3. In conclusion, our findings suggest inhibition of PRMT1 mitigates SI-AKI by inactivating the TGF-β1/Smad3 pathway in the cortex and IL-6/STAT3 pathway in the medulla. Our findings may aid in the identification of potential therapeutic target molecules for SI-AKI.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biofabrication
·
2020
·Vol. 12
·期 2
·025030
·
IF 8.213
Chong Wang,Haibing Yue,Wei Huang,Xudong Lin,Xiaoqiong Xie,Zhi He,Xiao He,Sanbiao Liu,Lu Bai,Bingheng Lu,Yen Wei,Min Wang
Due to the increasing aging population and the high probability of sport injury among young people nowadays, it is of great demand to repair/regenerate diseased/defected osteochondral tissue. Given that osteochondral tissue mainly consists of a subchondral layer and a cartilage layer which are structurally heterogeneous and mechanically distinct, developing a biomimetic bi-phasic scaffold with excellent bonding strength to regenerate osteochondral tissue is highly desirable. Three-dimensional (3D) printing is advantageous in producing scaffolds with customized shape, designed structure/composition gradients and hence can be used to produce heterogeneous scaffolds for osteochondral tissue regeneration. In this study, bi-layered osteochondral scaffolds were developed through cryogenic 3D printing, in which osteogenic peptide/β-tricalcium phosphate/poly(lactic-co-glycolic acid) water-in-oil composite emulsions were printed into hierarchically porous subchondral layer while poly(D,L-lactic acid-co-trimethylene carbonate) water-in-oil emulsions were printed into thermal-responsive cartilage frame on top of the subchondral layer. The cartilage frame was further filled/dispensed with transforming growth factor-β1 loaded collagen I hydrogel to form the cartilage module. Although the continuously constructed osteochondral scaffolds had distinct microscopic morphologies and varied mechanical properties at the subchondral zone and cartilage zone at 37 °C, respectively, the two layers were closely bonded together, showing excellent shear strength and peeling strength. Rat bone marrow derived mesenchymal stem cells (rBMSCs) exhibited high viability and proliferation at both subchondral- and cartilage layer. Moreover, gradient rBMSC osteogenic/chondrogenic differentiation was obtained in the osteochondral scaffolds. This proof-of-concept study provides a facile way to produce integrated osteochondral scaffolds for concurrently directing rBMSC osteogenic/chondrogenic differentiation at different regions.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2022
·
IF 5.195
Xiao-guo Suo,Fang Wang,Chuan-hui Xu,Xiao-yan He,Jia-nan Wang,Yao Zhang,Wei-jian Ni,Hao Lu,Ming-lu Ji,Yuan He,Shuai-shuai Xie,Ya-ru Yang,Jia-gen Wen,Juan Jin,Qian Gong,Jun Li,Ming-ming Liu,Xiao-ming Meng
Renal fibrosis , a common feature of chronic kidney disease , causes the progressive loss of renal function, in which TGF-β 1 plays a critical role. In this study, we found that expression levels of TGF-β 1 and its receptor 1 (TGF-βR1) were both significantly increased in obstructive fibrosis kidneys. AZ12601011 is a small molecular inhibitor of TGF-βR1; however, its therapeutic potential for renal fibrosis remains unclear. During the experiments, AZ12601011 was applied to various models of renal fibrosis followed by unilateral ureteral obstruction (UUO) and ischemia/reperfusion (I/R) in vivo , in addition to renal tubular epithelial cells (TECs) challenged by hypoxia/reoxygenation (H/R) and TGF-β 1 in vitro. Our results revealed that AZ12601011 ameliorated renal injuries and fibrosis shown by PAS, HE , and Masson staining , which was consistent with the decrease in Col-1 and α-SMA expression in the kidneys from UUO and I/R mice. Similarly, in vitro data showed that AZ12601011 inhibited the induction of Col-1 and α-SMA in both TECs treated with TGF-β 1 and H/R. In addition, the results of cellular thermal shift assay (CETSA), molecular docking , and western bolt indicated that AZ12601011 could directly bind to TGF-βR1 and block activation of the downstream Smad3. Taken together, our findings suggest that AZ12601011 can attenuate renal fibrosis by blocking the TGF-β/Smad3 signaling pathway and it might serve as a promising clinical candidate in the fight against fibrotic kidney diseases.
研究领域:
药理学
·
肾病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Cardiovascular Translational Research
·
2025
·
IF 2.5
Zhou Qiaofeng,Jiang Na,Li Shihuan,Li Suqin,Liu Jie,Yu Liangzhu,Liu Guoli,Xia Hongli,Li Mincai
Myocardial fibrosis (MF) severely impairs the heart structure and function post-myocardial infarction. The study investigated the effectiveness and mechanism of diammonium glycyrrhizinate (DG) on ISO-induced MF. ISO-stimulated mouse cardiac fibroblasts (CFs) were treated with DG to assess the proliferation, inflammation, and fibrosis markers (α-SMA, collagen, TGF-β1, Smad3). The MF model was induced in mice by administering ISO, followed by a 4-week treatment with DG (60 mg/kg/day). Cardiac function was measured using echocardiography, and histology and molecular analyses were performed. DG significantly suppressed the CF proliferation and reduced the expression of fibrotic markers. In ISO-treated mice, DG improved the cardiac function and attenuated the upregulated fibrosis markers. Molecular analysis revealed DG suppressed the TGF-β1/Smad3 pathway activation. The antifibrotic effect was enhanced when combined with STAT3 inhibition. DG effectively alleviates ISO-induced myocardial fibrosis dysfunction by inhibiting the STAT3/Smad3 signaling pathway, demonstrating its potential as a treatment for cardiac fibrosis. Graphical abstract
研究领域:
心脏病学
·
药理学
·
分子生物学
·
细胞生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2015
·
IF 3.088
Lin Zhu,Yu-Qing Zhang
N,O-Carboxymethyl chitosan (NOCC) can prevent postsurgical adhesion formation. Here, we described the preparation of a novel silkworm pupa NOCC and its effects on the prevention of postoperative adhesion in a rat cecal abrasion model. The degree of deacetylation (DDA) of silkworm pupa chitosan was only 49.87 ± 0.86%; regardless, it was used as the raw material to construct the novel silkworm pupa NOCC, which had a weaker crystallinity than the NOCC standard. Sixty male Sprague–Dawley rats were divided into three groups and treated as follows: 0.9% normal saline solution as a negative control, medical anti-adhesion gel as a positive control and the silkworm pupa NOCC anti-adhesion solution. Two and three weeks after surgery, the animals were killed and the adhesion formation was scored. The silkworm pupa NOCC solution significantly decreased the levels of WBC, TNF-α, IL-1β, IL-2, IL-6 and IL-8 but had no effect on IL-4. Additionally, a lower level of TGF-β 1 expression was found in the silkworm pupa NOCC group, and significantly less collagen ( P < 0.01) and fewer inflammatory cells and fibroblasts were detected in the animals of this group. These results suggested that the novel NOCC from silkworm pupa using the method described here have potential applications in the prevention of postoperative intestinal adhesion.
研究领域:
生物医学工程
·
药理学
·
外科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2026
·
IF 5.7
Yunhui Fu,Yuxi Li,Chenlu Wu,Yiying Chen,Xikui Tong,Chen Zhang,Meiyan Wang,yue Shen,Wenyun Zheng,Xingyuan Ma
Mesenchymal stem cell (MSC) transplantation has emerged as an effective approach for treating articular cartilage damage. However, unintended hypertrophy and fibrosis of the regenerated cartilage tissue markedly undermine the therapeutic effect. Herein, a two-factor delivery system, E60TK, based on the elastin-like protein ELP (VPGIG60, E60), co-delivering transforming growth factor β1 (TGF-β1) and kartogenin (KGN), was established to regulate stem cells from human exfoliated deciduous teeth (SHED)-directed cartilage differentiation and prevent cartilage hypertrophy and fibrosis. MTT and Alcian blue staining outcomes demonstrated that the fusion protein E60T composed of E60 and TGF-β1 was capable of effectively facilitating the proliferation and chondrogenic differentiation of SHED cells. Transmission electron microscope (TEM) and DLS findings revealed that the recombinant protein E60T could load KGN at physiological temperature to form nanoparticles E60TK, with particle sizes 241.2 ± 46.1 nm. The results of immunofluorescence and immunohistochemistry following chondrogenic differentiation suggested that E60TK could efficiently induce the chondrogenic differentiation of SHED and significantly suppress the expression of type X collagen. The hyaluronic acid methacrylamide (HAMA) hydrogel loading E60TK, E60TK-HAMA, exhibited excellent biocompatibility, presented an interconnected porous architecture, and was completely degraded within 2 weeks in vitro. In vivo experiments indicated that the E60TK-HAMA hydrogel with SHED encapsulated could effectively promote the formation of new cartilage and inhibit hypertrophy. All these results signified that E60TK was an effective system for regulating the directed chondrogenic differentiation of SHED.
✓ 已验证
DOI
PubMed
高影响因子
MEDICAL SCIENCE MONITOR
·
2018
·
IF 1.894
Xuechan Tang,Xiaoli Xie,Xin Wang,Yan Wang,Xiaoyu Jiang,Huiqing Jiang
Background Piwi-interacting RNA (piRNA) is the largest class of small non-coding RNA, which has also been identified in somatic tissues, and aberrant expression of piRNAs in tumor tissues may be implicated in carcinogenesis. piR-823 is increased in liver cirrhosis and hepatocellular carcinoma (HCC). However, there is no report on the function of piR-823 in hepatic stellate cells (HSCs) activation during hepatic fibrosis. The present study investigated the role of piR-823 in HSC activation. Matreial/Methods Liver fibrosis was induced in mice by carbon tetrachloride (CCL 4 ) injection and bile duct ligation (BDL). The primary HSCs were isolated from mice and cultured. The expression of piR-823 was measured by real-time PCR. The effect of piR-823 on HSCs was evaluated by either sense sequence or antisense sequence of piR-823 carried by liposome. Proteins binding to piR-823 were assayed by RNA pull-down technique and liquid chromatography-mass spectrometry (LC-MS). Results Our data for the first time show that piR-823 is significantly upregulated in activated HSCs. Overexpression of piR-823 promoted HSC proliferation, α-SMA and COL1a1 production, whereas inhibition of piR-823 suppressed the activity of HSCs. Interestingly, the combination of piR-823 and EIF3B promoted TGF-β1 expression. Conclusions Our data illustrate a novel mechanism of piR-823 in HSC activities. The combination of piR-823 and EIF3B increased TGF-β1 expression, which activates HSCs in liver fibrosis. piR-823 may be a new target in the treatment of liver fibrosis.
研究领域:
分子生物学
·
肝病学
·
细胞生物学
·
基因组学
✓ 已验证
DOI
PubMed
高影响因子
Scientific Reports
·
2026
·
IF 4.9
Yi Tingting,Xu Mei,Wang Lihua,Wang Pengwei
Recently, mesenchymal stem cells (MSCs), valued for their multipotent properties, have attracted significant attention in disease therapy. Transforming growth factor-β1(TGF-β1), a cytokine involved in regulating cellular stress responses, is closely associated with neurological function and the differentiation of MSCs. The primary purpose of this research was to assess the neuroprotective capacity of exosomes from TGF-β1-pretreated human umbilical cord mesenchymal stem cells (hUCMSCs) on neuronal injury in epilepsy. In this study, we established epileptic models using male C57BL/6 mice and hippocampal Neurons. Exosomes from TGF-β1- pretreated hUCMSCs were characterized via transmission electron microscopy (TEM) combined with nanoparticle tracking analysis (NTA) and were then applied as a therapeutic intervention. Our research demonstrated that TGF-β1 upregulated the level of the long non-coding RNA urothelial carcinoma-associated 1 (lncRNA UCA1) in hUCMSC-derived exosomes. Exosomes from TGF-β1-pretreated hUCMSCs enhanced neuronal viability, inhibited apoptosis, and reduced inflammation and oxidative stress levels, whereas UCA1 knockdown reversed these beneficial effects. Furthermore, lncRNA UCA1 directly binds to miR-132. Knockdown of UCA1 upregulated miR-132 levels and downregulated SIRT1 expression; this downregulation could be rescued by inhibiting miR-132. In vivo, we further observed that exosomes from TGF-β1-pretreated hUCMSCs alleviated neuronal damage in the hippocampal CA3 region, inhibited glial activation, and suppressed the increase of related inflammatory factors. In contrast, UCA1 knockdown produced the opposite effects. The in vivo findings paralleled the results of the in vitro cell experiments. In conclusion, these results demonstrated that exosomes from TGF-β1-pretreated hUCMSCs exert anti-epileptic effects by modulating the lncRNA UCA1 / miR-132 / SIRT1 axis.
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Endocrinology
·
2023
·
IF 5.2
Zhao Qingsong,Xu Jinmei,Han Xu,Zhang Zheqi,Qu Jiahui,Cheng Zhifeng
Background: Diabetic foot ulcer (DFU) represents a highly-prevalent complication of diabetes mellitus (DM). Herein, the current study sought to identify the role of growth differentiation factor 10 (GDF-10) in wound healing in DFU via regulation of the transforming growth factor-beta 1 (TGF-β1)/Smad3 pathway.Methods: DM- and DFU-related microarray datasets GSE29221 and GSE134431 were firstly retrieved, and weighted gene co-expression network analysis (WGCNA) was carried out to construct a co-expression network affecting wound healing in DFU, followed by differential analysis. A protein-protein interaction (PPI) network of the DFU-related genes was subsequently constructed, and the core genes and signaling pathways in DFU were screened with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional analyses. A DFU rat model was constructed for mechanism verification of the effect of GDF-10 on wound healing in DFU.Results: WGCNA screened five co-expression modules, and the brown module was most closely-related to DM. Clustering analysis screened 4417 candidate genes, of which 175 differential genes were associated with wound healing, further involved in TGF-β1/Smad3 signaling pathway regulation of wound healing in DFU. The PPI network analysis predicted that GDF-10 might regulate the TGF-β1/Smad3 signaling pathway to participate in DFU development. Results of animal experimentation showed that the wound healing rates of NFU, DFU, DFU + GDF and GDF + SIS3 groups on the 22nd day were (87.66 ± 6.80)%, (56.31 ± 7.29)%, (71.64 ± 9.43)% and (55.09 ± 7.13)%, respectively. Besides, the expression of TGF-β1 in NFU, DFU, DFU + GDF and GDF + SIS3 groups was 0.988 ± 0.086, 0.297 ± 0.036, 0.447 ± 0.044, and 0.240 ± 0.050, respectively, and that of Smad3 was 1.009 ± 0.137, 0.145 ± 0.017, 0.368 ± 0.048, and 0.200 ± 0.028, respectively. Specifically, GDF-10 exerted a significant diminishing effect on fasting blood glucose level, and promoted wound healing in DFU rats, in addition to up-regulation of VEGF, FGF, Ang-1, TGF-β1, Smad3 and enhancement of IL-1b, IL-6, TNF-a and MMP-9, thereby promoting fibroblast proliferation, collagen deposition and angiogenesis.Conclusions: Our findings highlight that GDF-10 may promote angiogenesis by activating TGF-β1/Smad3 signaling, thereby promoting wound healing in DFU rats.
✓ 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）