JOURNAL OF DERMATOLOGICAL TREATMENT
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2020
·
IF 2.156
Yifeng Xiao
Background This study explored the function and mechanism of miR-486-5p in HSFBs.Methods Qualitative real-time-polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-486-5p in HS and hypertrophic scar fibroblasts (HSFBs). Viability, migration, invasion ability, apoptosis, and expressions of Collagen I, Collagen III, α-SMA and Cleaved caspase-3 in HSFBs after transfection with miR-486-5p mimic or inhibitor were measured by CCK-8, wound-healing, transwell, and Western blot, respectively. Interaction between miR-486-5p and IGF1 was predicted by Targetscan version 7.2 and further confirmed by dual-luciferase assay, and functional rescue experiments were conducted to verify the predicted molecular mechanism. The activation of PI3K/AKT pathway was also analyzed by Western blot.Results MiR-486-5p was low-expressed in HS and HSFBs, and that overexpression of miR-486-5p suppressed the viability, migration, invasion, and expressions of Collagen I, Collagen III, and α-SMA of HSFBs, meanwhile, it also promoted apoptosis and Cleaved caspase-3 expression in HSFBs. Moreover, IGF1 was targeted by miR-486-5p, and increased viability, migration, invasion, and collagens expressions, the activation of PI3K/Akt pathway, and decreased apoptosis and Cleaved caspase-3 induced by miR-486-5p inhibitor could be partly alleviated by siIGF1.Conclusions Overexpressed miR-486-5p inhibited the hyperproliferation and excessive production of collagen in HSFBs via IGF1/PI3K/AKT pathway.
研究领域:
分子生物学
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细胞生物学
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皮肤病学
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PubMed
高影响因子
JOURNAL OF BONE AND MINERAL RESEARCH
·
2023
·Vol. 38
·期 4
·556-567
·
IF 6.2
Ruiye Bi,Xueting Luo,Qianli Li,Peiran Li,Haohan Li,Yi Fan,Binbin Ying,Songsong Zhu
Temporomandibular joint (TMJ) growth requires orchestrated interactions between various cell types. Recent studies revealed that fibrocartilage stem cells (FCSCs) in the TMJ cartilage play critical roles as cell resources for joint development and repair. However, the detailed molecular network that influences FCSC fate during TMJ cartilage development remains to be elucidated. Here, we investigate the functional role of Igf1 in FCSCs for TMJ cartilage growth and homeostasis by lineage tracing using Gli1-CreER + ; Tm flfl mice and conditional Igf1 deletion using Gli1-/Col2-CreER + ; Igf1 fl/fl mice. In Gli1-CreER + ; Tm flfl mice, red fluorescence + (RFP + ) FCSCs show a favorable proliferative capacity. Igf1 deletion in Gli1 + / Col2 + cell lineages leads to distinct pathological changes in TMJ cartilage. More serious cartilage thickness and cell density reductions are found in the superficial layers in Gli1-CreER + ; Igf1 fl/fl mice. After long-term Igf1 deletion, a severe disordered cell arrangement is found in both groups. When Igf1 is conditionally deleted in vivo, the red fluorescent protein-labeled Gli1 + FCSC shows a significant disruption of chondrogenic differentiation, cell proliferation, and apoptosis leading to TMJ cartilage disarrangement and subchondral bone loss. Immunostaining shows that pAkt signaling is blocked in all cartilage layers after the Gli1 + -specific deletion of Igf1 . In vitro, Igf1 deletion disrupts FCSC capacities, including proliferation and chondrogenesis. Moreover, the deletion of Igf1 in FCSCs significantly aggravates the joint osteoarthritis phenotype in the unilateral anterior crossbite mouse model, characterized by decreased cartilage thickness and cell numbers as well as a loss of extracellular matrix secretions. These findings uncover Igf1 as a regulator of TMJ cartilage growth and repair. The deletion of Igf1 disrupts the progenitor capacity of FCSCs, leading to a disordered cell distribution and exaggerating TMJ cartilage dysfunction. © 2023 American Society for Bone and Mineral Research (ASBMR).
研究领域:
发育生物学
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干细胞生物学
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骨科
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分子生物学
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病理学
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PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2021
·
IF 6.475
Ting Xia,Chang-Shun Liu,Yan-Nan Hu,Zhen-Ye Luo,Fei-Long Chen,Li-Xia Yuan,Xiao-Mei Tan
Type 2 diabetes mellitus (T2DM) has become a worldwide concern in recent years. Coix seed (CS) as a homologous substance of traditional Chinese medicine and food, its polysaccharides can improve the symptoms of patients with metabolic disorders. Since most plant polysaccharides are difficult to digest and absorb, we hypothesized that Coix seed polysaccharides (CSP) exert hypoglycemic effects through the gut. In this study, the underlying mechanisms regulating hypoglycemic effects of CSP on a T2DM mouse model were investigated. After treatment with CSP, serum insulin and high-density lipoprotein cholesterol levels were increased, while total cholesterol, triglycerides and low-density lipoprotein cholesterol levels were decreased in T2DM mice. In addition, CSP treatment helped repair the intestinal barrier and modulated the gut microbial composition in T2DM mice, mainly facilitating the growth of short-chain fatty acid (SCFA)-producing bacteria, Spearman’s analysis revealed these bacteria were positively related with the hypoglycemic efficacy of CSP. Colonic transcriptome analysis indicated the hypoglycemic effect of CSP was associated with the activation of the IGF1/PI3K/AKT signaling pathway. Correlative analysis revealed that this activation may result from the increase of SCFAs-producing bacteria by CSP. GC–MS detection verified that CSP treatment increased fecal SCFAs levels. Molecular docking revealed that SCFAs could bind with IGF1, PI3K, and AKT. Our findings demonstrated that CSP treatment modulates gut microbial composition, especially of the SCFAs-producing bacteria, activates the IGF1/PI3K/AKT signaling pathways, and exhibits hypoglycemic efficacy.
研究领域:
药理学
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内分泌学
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微生物学
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分子生物学
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营养学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2026
·Vol. 27
·期 11
·5013
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IF 5.6
Jiankang Bao,Xing Chen,Gang Zhai,Xia Jin,Jiangyan He,Zhan Yin,Qiyong Lou
Insulin-like growth factor 1 (IGF-1) signaling plays a complementary role to insulin signaling in glucose metabolism homeostasis. This study characterized the physiological roles of the IGF1 receptor A (Igf1ra) and B (Igf1rb) in zebrafish. The transcripts of igf1ra and igf1rb were detected in multiple zebrafish tissues, including the liver, muscle, and brain. Zebrafish lacking igf1ra or igf1rb were generated using CRISPR/Cas9 technology. Bothigf1ra−/−andigf1rb−/−zebrafish exhibited stunted growth. Reduced BMI was found inigf1ra−/−zebrafish, while BMI increased inigf1rb−/−zebrafish. Hyperglycemia and increased hepatic glycogen were observed inigf1ra−/−zebrafish, while blood glucose levels inigf1rb−/−zebrafish were normal. No significant difference in whole-body or hepatic triglyceride content was observed inigf1ra−/−zebrafish, while the whole-body and hepatic triglyceride content ofigf1rb−/−zebrafish increased compared to their wild-type control siblings. Further analyses of the expression patterns of key genes involved in glucose and lipid metabolism were conducted on igf1r mutants. Decreased levels of genes involved in glucose absorption and glycolysis and increased levels of genes involved in gluconeogenesis and glycogen synthesis were observed inigf1ra−/−zebrafish, but not inigf1rb−/−zebrafish. Conversely, significantly decreased levels of transcripts involved in lipolysis and increased levels of transcripts involved in the lipogenesis process were observed inigf1rb−/−zebrafish, but not inigf1ra−/−zebrafish. Restricted cell growth and protein synthesis signaling, including AKT and mTOR activation, was also detected inigf1ra−/−zebrafish, while a moderate elevation in AKT and mTOR activity was seen inigf1rb−/−zebrafish. Taken together, our results suggest that functional divergence occurred after the duplication of the zebrafish igf1r gene, with igf1ra primarily modulating glucose absorption and utilization, and igf1rb primarily affecting lipid metabolism in the somatotropic axis.
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高影响因子
Adipocyte
·
2023
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IF 3.3
Jiong Ma,Junyan Li,Xuejun Chen,Yanyan Ma
Background Platinum is a commonly used drug for ovarian cancer (OvCa) treatment, but drug resistance limits its clinical application. This study intended to delineate the effects of adipocytes on platinum resistance in OvCa.Methods OvCa cells were maintained in the adipocyte-conditioned medium. Cell viability and apoptosis were detected by CCK-8 and flow cytometry, separately. Proliferation and apoptosis-related protein expression were assayed by western blot. The IC50 values of cisplatin and carboplatin were determined using CCK-8. IGF1 secretion and expression were assayed via ELISA and western blot, respectively. A xenograft model was established, and pathological changes were detected by H&E staining. Proliferation and apoptosis-associated protein expression was assessed via IHC.Results Adipocytes promoted the viability and repressed cell apoptosis in OvCa, as well as enhancing platinum resistance, while the addition of IGF-1 R inhibitor reversed the effects of adipocytes on proliferation, apoptosis, and drug resistance of OvCa cells. Treatment with different concentrations of Ojeok-san (OJS) inhibited the adipocyte-induced platinum resistance in OvCa cells by suppressing IGF1. The combined treatment of OJS and cisplatin significantly inhibited tumour growth in vivo with good mouse tolerance.Conclusion In summary, OJS inhibited OvCa proliferation and platinum resistance by suppressing adipocyte paracrine IGF1 secretion.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-17
·
IF 9.429
Xu Kaiwei,Jin Lufei,Xu Liu,Zhu Yuchao,Hong Lu,Pan Chunshu,Li Yanying,Yao Junlie,Zou Ruifen,Tang Weiwei,Wang Jianhua,Wu Aiguo,Ren Wenzhi
Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest malignant tumors with features of matrix barrier caused poor drug permeability, and susceptibility to drug resistance. Herein, a PDAC and its stromal cell dual-targeted photothermal-chemotherapy strategy is explored to loosen the matrix and reverse drug resistance. To achieve this goal, black TiO2-Gd nanocomposites were conjugated with insulin like growth factor 1 (IGF1), and loaded with gemcitabine (GEM) to construct bTiO2-Gd-IGF1-GEM nanoprobes. In vitro results show that under 808 nm near-infrared irradiation, killing effect of the nanoprobes on drug-resistant MIA PaCa-2 cell is 3.3 times than that of GEM alone. In vivo experiments indicate the synergetic photothermal-chemotherapy not only loosens fibrous matrix of pancreatic tumor model, but also dramatically inhibits tumor growth, and almost completely eradicates the tumor after 12 days of treatment. In addition, relaxation rate of the nanoprobes is 8.2 times than commercial contrast agent Magnevist, therefore boosts the signal of magnetic resonance imaging in pancreatic tumor. In conclusion, our results reinforce that the prepared nanoprobes are promising to break matrix barrier and overcome drug resistance in PDAC.
研究领域:
肿瘤学
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纳米技术
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生物医学工程
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癌症治疗
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医学影像
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2026
·
IF 5.4
Wentong Wu,Zhaoce Zheng,Danping Wang,Ming Shan,Jing Han,Dongqing Jing,Chunjng Liang,Xi Zhang,Jinxin Liu
Background and Aims Ferulic acid (FA) exerts anti-atherosclerotic effects, but the underlying mechanisms remain incompletely understood. The present study investigated whether smooth muscle cell (SMC)-derived insulin-like growth factor 1 (IGF1) mediate FA’s protective effects by regulating lysosome-associated membrane protein 2 (LAMP2), inflammatory cytokines, and matrix metalloproteinase 3 (MMP3). Methods Male ApoE −/− mice were fed a high-fat diet for 8 weeks to established atherosclerosis models and then treated with FA (40 mg/kg/d). SMC-specific Igf1 knockout (SMC- Igf1 -KO) mice were generated to determine cell-type-specific requirements. In vitro , SMC-derived foam cells were induced by oxidized low-density lipoprotein (ox-LDL) and treated with FA ± IGF1 receptor (IGF1R) inhibitor. Plaque area, lipid deposition, and expression of IGF1, LAMP2, interleukin (IL)-6, IL-4, and MMP3 were assessed by en face staining, histology, Western blot, quantitative real-time PCR (qRT-PCR), and immunofluorescence selected as needed. Results FA treatment significantly reduced atherosclerotic plaque area and lipid deposition in male ApoE −/− mice, accompanied by upregulated IGF1 and downregulated 45 kDa-LAMP2 expression in aortic lesions. FA also increased IL-4 expression and decreased IL-6 and MMP3 expression. SMC-IGF1-KO significantly weakened the protective effects of FA. In vitro , FA increased IGF1 expression and IGF1R phosphorylation, reduced 45 kDa-LAMP2, IL-6, and MMP3 expression, and increased IL-4 expression in ox-LDL-induced SMC-derived foam cells. These effects were reversed by IGF1R inhibition. Conclusion FA treatment significantly attenuates atherosclerosis. It partly resulted from that SMC-derived IGF1-mediated suppression of a 45 kDa-LAMP2 isoform, along with modulation of inflammatory balance (IL-6/IL-4) and MMP3 expression. The SMC-IGF1/45 kDa-LAMP2 axis may represent a potential therapeutic target for atherosclerosis.
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高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·
IF 6.7
Kangle Li,Hongjie Cui,Si Wang,Qianfu Gan,Qinghua Liu,Shuangbo Huang
Alterations in gut microbiota and its metabolites are associated with placental and fetal development. Although proline has been shown to enhance placental function and improve pregnancy outcomes, its interaction with the gut microbiota remains poorly understood. In this study, a gestational low-protein diet (LPD) leads to decreased fetal birth weight and impaired placental vascular development, as well as increased embryonic resorption rates; these effects are mitigated by dietary proline supplementation. Mechanistically, proline enhances the abundance of Akkermansia and the production of butyrate in the gut, thereby promoting placental angiogenesis by activating the placental Wnt/insulin-like growth factor 1 (Igf1) signaling pathway, ultimately alleviating fetal developmental impairment caused by LPD. Moreover, in an in vitro porcine vascular endothelial cell model under amino acid-restricted conditions, butyrate enhances angiogenesis by activating the Wnt/Igf1 signaling pathway. These findings reveal that targeting the dietary proline supply and gut microbiota may open new avenues for the prevention of intrauterine growth restriction.
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高影响因子
Molecular Medicine Reports
·
2020
·Vol. 22
·期 6
·5053-5068
·
IF 2.1
Guofang Guan,Xiao He,Jingjing Chen,Li Bin,Xuxia Tang
Sensorineural hearing loss is prevalent in patients receiving cisplatin therapy. Tetramethylpyrazine (Tet) and tanshinone IIA (Tan IIA) have protective roles against hearing impairment or ototoxicity. The present study aimed to investigate the molecular mechanisms underlying cisplatin‑induced ototoxicity and the protective effect of Tet and Tan IIA against it. House Ear Institute‑Organ of Corti 1 auditory cells were treated with titrating doses of Tan IIA, Tet, and cisplatin. In a cell viability assay, cisplatin, Tan IIA and Tet had IC50 values of 42.89 µM, 151.80 and 1.04x103 mg/l, respectively. Tan IIA augmented cisplatin‑induced cytotoxicity. However, Tet concentrations <75 mg/l attenuated cisplatin‑induced cytotoxicity and apoptosis. Moreover, RNA sequencing analysis was carried out on auditory cells treated for 30 h with 30 µM cisplatin alone for 48 h or combined with 37.5 mg/l Tet for 30 h. Differentially expressed genes (DEGs) induced in these conditions were identified and examined using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Cisplatin increased the expression of genes related to the p53 and FoxO pathways, such as Fas, p21/CDKN1A, and Bcl‑2 binding component 3, but decreased the expression of insulin‑like growth factor 1 (IGF1), as well as genes in the histone (Hist)1 and Hist2 clusters. Treatment with Tet downregulated FOXO3 and Bcl‑2 binding component 3, and increased the expression of IGF1. Moreover, Tet upregulated genes associated with Wnt signaling, but not p53‑related genes. Thus, the otoprotective properties of Tet might be mediated by activation of Wnt and IGF1 signaling, and inhibition of FoxO signaling.
研究领域:
药理学
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耳鼻喉科学
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分子生物学
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基因组学
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高影响因子
Scientific Reports
·
2021
·Vol. 11
·期 1
·1-13
·
IF 4.38
Jiao Jianhang,Peng Chuangang,Li Chen,Qi Zhiping,Zhan Jing,Pan Su
Electrospun fibrous scaffolds combined with bioactive factors can display impressive performance as an ideal wound dressing, since they can mimic the composition and physicochemical properties of the extracellular matrix (ECM). The aim of this study was to fabricate a new composite biomaterial (IGF1-DA and Os-DA-modified PLGA electrospun fibrous scaffold) for wound healing, using a rat model for experimental evaluation. A small pentapeptide tag composed of DA–Lys–DA–Lys–DA residues was introduced into insulin-like growth factor 1 (IGF1) and the antimicrobial peptide Os to prepare IGF1 and Os modified with 3,4-dihydroxyphenylalanine (DA) (IGF1-DA and Os-DA). The designed chimeric growth factor and antimicrobial peptide could successfully anchor to PLGA electrospun fibrous scaffolds, and the growth factor and antimicrobial peptide could be controllably released from the electrospun fibrous scaffolds. The results showed that the IGF1-DA and Os-DA-modified PLGA electrospun fibrous scaffolds (PLGA/Os-DA/IGF1-DA) exhibited high hydrophilicity and antimicrobial activity; moreover, the porous network of the scaffolds was similar to that of the natural ECM, which can provide a favourable environment for BALB/C 3T3 cells growth. The in vivo application of PLGA/Os-DA/IGF1-DA electrospun fibrous scaffolds in rat skin wounds resulted in improved wound recovery and tissue regeneration rate. The experimental results indicated that the IGF1-DA and Os-DA could effectively bind to PLGA electrospun fibrous scaffolds, promote wound healing and prevent infection in rats, thereby suggesting that PLGA/Os-DA/IGF1-DA electrospun fibrous scaffolds have a wide application value in the field of skin wound repair.
研究领域:
生物医学工程
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组织工程
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材料科学
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伤口愈合研究
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PubMed
高影响因子
Nano Research
·
2023
·
IF 9.9
Li Yueyue,Zhong Weifeng,Wu Junjie,Jia Yuan,Chen Zhonghua,Zhang Kaiwen,Guo Danyang,Fu Yifei,Chen Mengnan,Chen Weiwei,Tian Fan,Li Xia,Zhang Hongji,Zhou Xiaojin,Yuan Feng-Lai
The recruitment of key cells to regeneration sites is a promising strategy to promote functional wound healing. Dermal fibroblasts exhibit a heterogeneous population of cells during homeostasis and in response to injury. Papillary fibroblasts play central regulatory roles in the regeneration of skin appendages during wound healing. Inspired by the phenomenon where bait for grass carp can attract grouped grass carps to a fishing spot soon, “Grass Carp Fishing” multifunctional hydrogels, that is, codelivery of an antibody of leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1) on the surface of papillary fibroblasts and insulin-like growth factor 1 (IGF1) with recruitment function, can recruit papillary fibroblasts. In the experiments, carboxymethyl chitosan showed positive effects in promoting cell proliferation and neovascularization, while dopamine-grafted gelatin was effective in stabilizing the structure and prolonging the degradation time. The sustained release of Lrig1 antibodies and IGF1 from injectable self-healing multifunctional hydrogels persistently accelerated the migration and proliferation of Lrig1 + fibroblasts. The in vivo results from a full-thickness cutaneous wound model showed that injectable self-healing multifunctional hydrogel accelerated wound healing and skin regeneration through the recruitment of Lrig1 + papillary fibroblasts in wound tissue. Our findings reveal an injectable self-healing multifunctional hydrogel for regeneration, a promising approach to promoting skin wound healing.
研究领域:
生物医学工程
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组织工程
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伤口愈合
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再生医学
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高影响因子
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