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Ovarian cancer is the most lethal gynecologic malignancy, due to its high propensity for metastasis. Cancer-associated fibroblasts, as the dominant component of tumor microenvironment, are crucial for tumor progression. However, the mechanisms underlying the regulation of ovarian cancer cells by cancer-associated fibroblasts remain little known. Here, we first isolated cancer-associated fibroblasts from patients’ ovarian tissues and found that cancer-associated fibroblasts promoted SKOV3 cells’ proliferation, migration, and invasion. Fibroblast growth factor-1 was identified as a highly increased factor in cancer-associated fibroblasts compared with normal fibroblasts by quantitative reverse transcription polymerase chain reaction (~4.6-fold, p < 0.01) and ELISA assays (~4-fold, p < 0.01). High expression of fibroblast growth factor-1 in cancer-associated fibroblasts either naturally or through gene recombination led to phosphorylation of fibroblast growth factor receptor 4 in SKOV3 cells, which is followed by the activation of mitogen-activated protein kinase/extracellular signal–regulated protein kinase pathway and epithelial-to-mesenchymal transition–associated gene Snail1 and MMP3 expression. Moreover, treatment of SKOV3 cell with fibroblast growth factor receptor inhibitor PD173074 terminated cellular proliferation, migration, and invasion, reduced the phosphorylation level of fibroblast growth factor receptor 4, and suppressed the activation of mitogen-activated protein kinase/extracellular signal–regulated protein kinase pathway. In addition, the expression level of Snail1 and MMP3 was reduced, while the expression level of E-cadherin increased. These observations suggest a crucial role for cancer-associated fibroblasts and fibroblast growth factor-1/fibroblast growth factor receptor 4 signaling in the progression of ovarian cancer. Therefore, this fibroblast growth factor-1/fibroblast growth factor receptor 4 axis may become a potential target for the treatment of ovarian cancer.

Diabetic retinopathy (DR) severely affects vision in individuals with diabetes. High glucose (HG) induces oxidative stress in retinal cells, a key contributor to DR development. Previous studies suggest that fibroblast growth factor-1 (FGF-1) can mitigate hyperglycemia and protect tissues from HG-induced damage. However, the specific effects and mechanisms of FGF-1 on DR remain unclear. In our study, FGF-1-pretreated adult retinal pigment epithelial (ARPE)-19 cells were employed to investigate. Results indicate that FGF-1 significantly attenuated HG-induced oxidative stress, including reactive oxygen species, DNA damage, protein carbonyl content, and lipid peroxidation. FGF-1 also modulated the expression of oxidative and antioxidative enzymes. Mechanistic investigations showed that HG induced high endoplasmic reticulum (ER) stress and upregulated specific proteins associated with apoptosis. FGF-1 effectively alleviated ER stress, reduced apoptosis, and restored autophagy through the adenosine monophosphate-activated protein kinase/mammalian target of the rapamycin signaling pathway. We observed that the changes induced by HG were dose-dependently reversed by FGF-1. Higher concentrations of FGF-1 (5 and 10 ng/mL) exhibited increased effectiveness in mitigating HG-induced damage, reaching statistical significance (p < 0.05). In conclusion, our study underscores the promising potential of FGF-1 as a safeguard against DR. FGF-1 emerges as a formidable intervention, attenuating oxidative stress, ER stress, and apoptosis, while concurrently promoting autophagy. This multifaceted impact positions FGF-1 as a compelling candidate for alleviating retinal cell damage in the complex pathogenesis of DR.

Insulin resistance is associated with a greatly increased risk of type 2 diabetes. Administration of fibroblast growth factor-1 (FGF-1) resulted in a marked improvement in insulin sensitivity. However, the underlying molecular mechanism whereby FGF-1 represses insulin resistance remains largely unknown. Here, we sought to delineate the role of FGF-1 in insulin resistance with respect to its anti-inflammatory capability. In this study, we found that FGF-1 had positive effects on glucose intolerance, hepatic lipid accumulation, and insulin resistance, while it markedly repressed cytokine secretion (TNF-α and IL-6) in serum and reduced liver inflammation in diet-induced obesity (DIO) mice. Further, FGF-1 treatment significantly represses TNF-α-induced insulin resistance and . These results indicate that FGF-1 likely ameliorates insulin resistance a mechanism that is independent of its glucose-lowering activity. Subsequent experiments demonstrated that FGF-1 ameliorated insulin resistance, and inflammation was accompanied by decreased c-Jun N-terminal kinase (JNK) signaling. In addition, it is likely that FGF-1 impedes JNK phosphorylation blocking the transforming growth factor-β activated kinase 1 (TAK1) and TAK1 binding protein 1 (TAB1) interaction. These findings reveal that FGF-1 regulates insulin sensitivity and may represent an attractive therapeutic target for preventing the development of insulin resistance.

Background In the field of diabetes research, many studies on cell therapy have been conducted using mesenchymal stem cells. This research was intended to shed light on the influence of canine adipose-tissue-derived mesenchymal stem cell conditioned medium (cAT-MSC CM) on in vitro insulin resistance models that were induced in differentiated 3T3-L1 adipocytes and the possible mechanisms involved in the phenomenon. Results Gene expression levels of insulin receptor substrate-1 (IRS-1) and glucose transporter type 4 (GLUT4) were used as indicators of insulin resistance. Relative protein expression levels of IRS-1 and GLUT4 were augmented in the cAT-MSC CM treatment group compared to insulin resistance models, indicating beneficial effects of cAT-MSC to DM, probably by actions of secreting factors. With reference to previous studies on fibroblast growth factor-1 (FGF1), we proposed FGF1 as a key contributing factor to the mechanism of action. We added anti-FGF1 neutralizing antibody to the CM-treated insulin resistance models. As a result, significantly diminished protein levels of IRS-1 and GLUT4 were observed, supporting our assumption. Similar results were observed in glucose uptake assay. Conclusions Accordingly, this study advocated the potential of FGF-1 from cAT-MSC CM as an alternative insulin sensitizer and discovered a signalling factor associated with the paracrine effects of cAT-MSC.

Alternatively activated macrophages (M2 macrophages) promote central nervous system regeneration. Our previous study demonstrated that treatment with peripheral nerve grafts and fibroblast growth factor-1 recruited more M2 macrophages and improved partial functional recovery in spinal cord transected rats. The migration of macrophages is matrix metalloproteinase (MMP) dependent. We used a general inhibitor of MMPs to influence macrophage migration, and we examined the migration of macrophage populations and changes in spinal function. Rat spinal cords were completely transected at T8, and 5 mm of spinal cord was removed (group T). In group R, spinal cord-transected rats received treatment with fibroblast growth factor-1 and peripheral nerve grafts. In group RG, rats received the same treatment as group R with the addition of 200 μM GM6001 (an MMP inhibitor) to the fibrin mix. We found that MMP-9, but not MMP-2, was upregulated in the graft area of rats in group R. Local application of the MMP inhibitor resulted in a reduction in the ratio of arginase-1 (M2 macrophage subset)/inducible nitric oxide synthase-postive cells. When the MMP inhibitor was applied at 8 weeks postoperation, the partial functional recovery observed in group R was lost. This effect was accompanied by a decrease in brain-derived neurotrophic factor levels in the nerve graft. These results suggested that the arginase-1 positive population in spinal cord transected rats is a migratory cell population rather than the phenotypic conversion of early iNOS+ cells and that the migration of the arginase-1+ population could be regulated locally. Simultaneous application of MMP inhibitors or promotion of MMP activity for spinal cord injury needs to be considered if the coadministered treatment involves M2 recruitment.

There is a need for a strategy to reduce scarring in meshed skin graft healing leading to a better cosmetic result without a significant increase in cost. The strategy in this paper is to increase the closure rate of a meshed skin graft to reduce scarring, which should also decrease the infection rate. Specifically, we used fibrin glue to attach all parts of the graft to the wound bed and added in an angiogenic growth factor and made the fibrin porous to further help the growth of blood vessels from the wound bed into the graft. There was a 10-day animal study and a one-month clinical study. Neither making the fibrin porous or adding an angiogenic agent (i.e., fibroblast growth factor-1 (FGF-1)) seemed to make a significant improvement in vivo or clinically. The use of fibrin on a meshed skin graft appears to speed up the regenerative healing rate leading to less scarring in the holes in the mesh. It appears to shorten the healing time by five days and keep the tissue stiffness close to normal levels vs. the doubling of the stiffness by the controls. A larger clinical study, however, is needed to definitively prove this benefit as well as the mechanism for this improvement.

Aim: To investigate whether sphingosine-1-phosphate (S1P), a potent angiogenic factor, induced vascular endothelial growth factor-C (VEGF-C) expression in endothelial cells in vitro and to examine its underlying mechanisms. Methods: Human umbilical vein endothelial cells (HUVECs) were examined. VEGF-C mRNA expression in the cells was assessed using real-time PCR. VEGF-C protein and FGFR-1 phosphorylation in the cells were measured with ELISA. RNA interference was used to downregulate the expression of matrix metalloproteinase-2 (MMP-2), fibroblast growth factor-1 (FGF-1) and FGF receptor-1 (FGFR-1). Results: Incubation of HUVECs with S1P (1, 5, and 10 μmol/L) significantly increased VEGF-C expression. The effect was blocked by pretreatment with the MMP inhibitor GM6001 or the FGFR inhibitor SU5402, but not the EGFR inhibitor AG1478. The effect was also blocked in HUVECs that were transfected with FGFR-1 or MMP-2 siRNA. Furthermore, incubation of HUVECs with S1P (5 μmol/L) significantly increased FGFR-1 phosphorylation, which was blocked by GM6001. Moreover, knockdown of FGF-1, not FGF-2, in HUVECs with siRNAs, blocked S1P-induced VEGF-C expression. Conclusion: S1P induces VEGF-C expression through a MMP-2/ FGF-1/FGFR-1-dependent pathway in HUVECs.

Ectopic pregnancy (EP) is defined as embryo implantation in a location other than the uterine cavity. We aimed to evaluate the expression of several genes, which may play a role in EP, in the ampulla region of fallopian tubes and endometrial tissue of women with EP. In this case-control study, 5 women who underwent salpingectomy due to EP, comprised the 5 pseudo-pregnant women as a control group. These participants referred to the Royan Institute, Shariati, and Arash hospital, Tehran, Iran during 2019-2021. We evaluated the expressions of vascular endothelial growth factor A mucin-1 colony-stimulating factor-1 heparin-binding epidermal growth factor-like growth factor and fibroblast growth factor 2 genes in the fallopian tube and endometrium of EP cases by real-time polymerase chain reaction using specific primers. The vascular endothelial growth factor expression was significantly higher in the ampulla region of the controls. However, no significant differences were observed in endometrial tissue. Assessments of colony-stimulating factor-1 and fibroblast growth factor 2 showed no significant differences between the case and control groups. showed significantly higher expression in the ampulla region of EP cases, but no significant difference was observed in expression in the endometrial tissues of the study groups. Mucin-1expression was significantly higher in both study regions of the EP cases. Our results have strongly suggested that these genes play important roles in proper implantation, and disruptions in their expression patterns could lead to EP. However, more studies are needed to confirm the current findings.

Background Acidic fibroblast growth factor (FGF‐1) has been identified as a potent mitogen for vascular cells, inducing formation of mature blood vessels in vitro and in vivo and represents one of the most promising approaches for the treatment of ischemic cardiovascular diseases by gene therapy. Nevertheless, and most probably due to the few experimental models able to address the issue, no study has described the therapeutic effects of FGF‐1 gene transfer in subjects with peripheral arterial disease (PAD) exhibiting a clinically relevant cardiovascular pathology. Methods In order to assess the potency of FGF‐1 gene transfer for therapeutic angiogenesis in ischemic skeletal muscles displaying decreased gene expression levels and sustained impaired formation of collateral vessels and arterioles, we developed a model of PAD in hamsters with a background of hypercholesterolemia. Hamsters fed a cholesterol‐rich diet and subjected to hindlimb ischemia exhibit a sustained impaired angiogenic response, as evidenced by decreased angiographic score and histological quantification of arterioles in the ischemic muscles. Results In this model, we demonstrate that NV1FGF (a human FGF‐1 expression plasmid), given intramuscularly 14 days after induction of hindlimb ischemia, promoted the formation of both collateral vessels and arterioles 14 days after treatment (i.e. 28 days post‐ischemia). Conclusions Our data provide evidence that NV1FGF can reverse the cholesterol‐induced impairment of revascularization in a hamster model of hindlimb ischemia by promoting the growth of both collateral vessels and arterioles in ischemic muscles exhibiting significantly decreased levels of gene expression compared with control muscles. Therefore, this study underscores the relevance of NV1FGF gene therapy to overcome perfusion defects in patients with PAD. Copyright © 2004 John Wiley & Sons, Ltd.

Through site-directed mutagenesis we have created a favorable fibroblast growth factor-1 (FGF-1) mutant (S130K) and linked it to a heparin-binding growth-associated molecule (HBGAM) to form the chimera S130K-HBGAM creating a heparin-independent, endothelial cell (EC)-specific mitogen. The proliferative responses of primary canine carotid artery smooth muscle cells (SMC) and jugular vein EC to FGF-1, S130K, or S130K-HBGAM, with and without heparin (5 U/mL), was quantitated by measuring tritiated thymidine uptake over 24 hours and expressing the results as percent of positive control (20% fetal bovine serum [FBS]) for group comparison. Unlike FGF-1, both S130K and S130K-HBGAM are heparin-independent mitogens for EC and SMC. S130K-HBGAM was equivalent to FGF-1 with heparin at 6 nmol/L. S130K-HBGAM did not demonstrate relative EC specificity in this assay. At higher concentrations, S130K-HBGAM is a potent, heparin-independent EC and SMC mitogen. Co-culture assays and in vivo delivery models may demonstrate EC specificity not identified in this single cell type proliferation assay.