scholarly journals Fibroblast Growth Factor-9 Activates c-Kit Progenitor Cells and Enhances Angiogenesis in the Infarcted Diabetic Heart

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Dinender Singla ◽  
Jing Wang
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Progenitor Cells ◽  
Cell Activation ◽  
Left Ventricular ◽  
Diabetic Heart ◽  
Fibroblast Growth ◽  
Sham Surgery ◽  
Left Ventricular Output ◽  
Fractional Shortening

We hypothesized that fibroblast growth factor-9 (FGF-9) would enhance angiogenesis via activating c-kit positive stem cells in the infarcted nondiabetic and diabetic heart. In brief, animals were divided into three groups: Sham, MI, and MI+FGF-9. Two weeks following MI or sham surgery, our data suggest that treatment with FGF-9 significantly diminished vascular apoptosis compared to the MI group in both C57BL/6 and db/db mice (p<0.05). Additionally, the number of c-kit+ve/SMα-actin+vecells and c-kit+ve/CD31+vecells were greatly enhanced in the MI+FGF-9 groups relative to the MI suggesting FGF-9 enhances c-Kit cell activation and their differentiation into vascular smooth muscle cells and endothelial cells, respectively (p<0.05). Histology shows that the total number of vessels were quantified for all groups and our data suggest that the FGF-9 treated groups had significantly more vessels than their MI counterparts (p<0.05). Finally, echocardiographic data suggests a significant improvement in left ventricular output, as indicated by fractional shortening and ejection fraction in both nondiabetic and diabetic animals treated with FGF-9 (p<0.05). Overall, our data suggests FGF-9 has the potential to attenuate vascular cell apoptosis, activate c-Kit progenitor cells, and enhance angiogenesis and neovascularization in C57BL/6 and db/db mice leading to improved cardiac function.

scholarly journals Lipocalin 2 stimulates bone fibroblast growth factor 23 production in chronic kidney disease

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Guillaume Courbon ◽  
Connor Francis ◽  
Claire Gerber ◽  
Samantha Neuburg ◽  
Xueyan Wang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Fibroblast Growth Factor ◽  
Kidney Function ◽  
Fibroblast Growth Factor 23 ◽  
Left Ventricular ◽  
Fibroblast Growth ◽  
Lipocalin 2

AbstractBone-produced fibroblast growth factor 23 (FGF23) increases in response to inflammation and iron deficiency and contributes to cardiovascular mortality in chronic kidney disease (CKD). Neutrophil gelatinase-associated lipocalin (NGAL or lipocalin 2; LCN2 the murine homolog) is a pro-inflammatory and iron-shuttling molecule that is secreted in response to kidney injury and may promote CKD progression. We investigated bone FGF23 regulation by circulating LCN2. At 23 weeks, Col4a3KO mice showed impaired kidney function, increased levels of kidney and serum LCN2, increased bone and serum FGF23, anemia, and left ventricular hypertrophy (LVH). Deletion of Lcn2 in CKD mice did not improve kidney function or anemia but prevented the development of LVH and improved survival in association with marked reductions in serum FGF23. Lcn2 deletion specifically prevented FGF23 elevations in response to inflammation, but not iron deficiency or phosphate, and administration of LCN2 increased serum FGF23 in healthy and CKD mice by stimulating Fgf23 transcription via activation of cAMP-mediated signaling in bone cells. These results show that kidney-produced LCN2 is an important mediator of increased FGF23 production by bone in response to inflammation and in CKD. LCN2 inhibition might represent a potential therapeutic approach to lower FGF23 and improve outcomes in CKD.

scholarly journals Fibroblast growth factor 23 (FGF23) level is associated with ultrafiltration rate in patients on hemodialysis

2020 ◽  
Author(s):  
Yoko Nishizawa ◽  
Yumi Hosoda ◽  
Ai Horimoto ◽  
Kiyotsugu Omae ◽  
Kyoko Ito ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Univariate Analysis ◽  
Hemodialysis Patients ◽  
Left Ventricular ◽  
Fibroblast Growth ◽  
Ultrafiltration Rate ◽  
Dialysis Duration ◽  
The Mean

Abstract Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates renal phosphate reabsorption and vitamin D synthesis in renal proximal tubules. High circulating FGF23 levels are associated with increased mortality in patients with chronic kidney disease and those on dialysis. Current data also suggest higher circulating levels of FGF23 are associated with cardiovascular mortality, vascular calcification, and left ventricular hypertrophy; however, evidence on the role of FGF23 in patients on dialysis is incomplete, and some of the data, especially those on cardiovascular disease (CVD), are controversial. This study aimed to evaluate factors associated with FGF23 in hemodialysis patients with or without CVD. Randomly selected 76 patients on maintenance hemodialysis at a single hemodialysis center were enrolled. After the exclusion of eight patients with extremely outlying FGF23 levels, 68 patients, including 48 males and 46 patients with a CVD history, were included in the study. The mean age was 64.4 ± 12.1 years, and the mean dialysis duration was 12.7 ± 7.1 years. Dialysis duration, time-averaged concentration of urea (TAC-urea), ultrafiltration rate (UFR), blood pressure during hemodialysis session, laboratory data, and echocardiographic parameters including interventricular septum thickness (IVST), left ventricular mass indices (LVMI), and ejection fraction were included in univariate and multivariate analyses. The median lgFGF23 levels in the overall cohort and in those with and without CVD were 2.14 (interquartile range, IQR − 0.43 to − 4.23), 2.01 (− 0.52 to 4.12), and 2.59 (0.07 to 4.32), respectively, and there was no difference between the patients with and without CVD (p = 0.14). The univariate analysis revealed that FGF23 was significantly associated with age (r =  − 0.12, p < 0.01), duration of hemodialysis (r =  − 0.11, p < 0.01), TAC-urea (r = 0.29, p = 0.01), UFR (r = 0.26, p = 0.04), alkaline phosphatase (ALP; r =  − 0.27, p = 0.03), corrected serum calcium (cCa; r = 0.32, p < 0.01), serum phosphate (iP, r = 0.57, p < 0.01), intact parathyroid hormone (iPTH; r = 0.38, p < 0.01), IVST (r = 0.30, p = 0.01), and LVMI (r = 0.26, p = 0.04). In multivariate regression analysis, FGF23 was significantly associated with cCa (F = 25.6, p < 0.01), iP (F = 22.5, p < 0.01), iPTH (F = 19.2, p < 0.01), ALP (F = 5.34, p = 0.03), and UFR (F = 3.94, p = 0.05). In addition, the univariate analysis after the categorization of patients according to CVD indicated that FGF23 was significantly associated with cCa (r = 0.34, p = 0.02), iP (r = 0.41, p < 0.01), iPTH (r = 0.39, p = 0.01), and TAC-urea (r = 0.45, p < 0.01) in patients with CVD, whereas only IVST (r = 0.53, p = 0.04) was associated with FGF23 in those without CVD. FGF23 levels in hemodialysis patients were extremely high and associated not only with mineral bone disease-related factors but also with UFR. Additionally, dialysis efficacy might be associated with lower FGF23 levels in patients with CVD.

scholarly journals Fibroblast growth factor-23 is associated with imaging markers of diabetic cardiomyopathy and anti-diabetic therapeutics

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Martin H. Sørensen ◽  
Annemie S. Bojer ◽  
Niklas R. Jørgensen ◽  
David A. Broadbent ◽  
Sven Plein ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Kidney Function ◽  
Fibroblast Growth Factor 23 ◽  
Left Ventricular ◽  
Fibroblast Growth ◽  
Cardiovascular Morbidity And Mortality ◽  
Fgf 23

Abstract Background The biomarker fibroblast growth factor-23 (FGF-23) has been associated with increased cardiovascular morbidity and mortality in both patients with and without type 2 diabetes. The aim of this study was to evaluate the relationship between FGF-23 and cardiac structure, function and perfusion in patients with type 2 diabetes and normal or mildly impaired kidney function. Furthermore, to investigate the association between FGF-23, anti-diabetes therapy and the classic complications and risk factors associated with type 2 diabetes. Methods In this cross-sectional study, 246 patients with type 2 diabetes underwent echocardiography and advanced cardiac magnetic resonance imaging to assess left ventricular (LV) structure and function. In addition, myocardial blood flow (MBF) during rest and pharmacological stress (adenosine 140 µg/kg/min) were evaluated in 183 of the patients. Patients with eGFR < 60 ml/min/1.73 m2 were excluded. Results Median (Q1–Q3) FGF-23 was 74 (58–91) ng/L. Patients with FGF-23 above the median had lower MBF during stress (2.3 ± 0.9 vs. 2.7 ± 0.9 ml/min/g, P = 0.001) and lower overall myocardial perfusion reserve (MPR) (2.7 ± 0.8 vs. 3.3 ± 1.1, P < 0.001). LV mass (143 ± 40 vs. 138 ± 36 g, P = 0.04) and E/e* (8.5 ± 3.2 vs. 7.6 ± 2.7, P = 0.04) were higher in patients with FGF-23 above the median. In a linear model adjusted for age, sex, eGFR and hypertension, increasing FGF-23 was associated with decreased MPR (P < 0.01, R2 = 0.11) and increased E/e* (P < 0.01, R2 = 0.07). FGF-23 was lower in patients receiving glucagon like peptide-1 (GLP-1) analogues (71 (57–86) vs. 80 (60–98) ng/L, P = 0.01) than in those who did not receive GLP-1 analogues. Conclusions In patients with type 2 diabetes and normal or mildly impaired kidney function, increased levels of FGF-23 are associated with impaired cardiac diastolic function and decreased MPR, caused by a decrease in maximal MBF during stress. Use of GLP-1 analogues is associated with decreased levels of FGF-23. Clinical trial registrationhttps://www.clinicaltrials.gov. Unique identifier: NCT02684331. Date of registration: February 18, 2016

Morphological Differentiation of Astroglial Progenitor Cells from Egf-Responsive Neurospheres in Response to Fetal Calf Serum, Basic Fibroblast Growth Factor, and Retinol

1996 ◽  
Vol 5 (2) ◽  
pp. 179-189 ◽  
Author(s):  
Yung H. Chiang ◽  
Vincenzo Silani ◽  
Feng C. Zhou
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Progenitor Cells ◽  
Basic Fibroblast Growth Factor ◽  
Calf Serum ◽  
Basal Medium ◽  
Morphological Differentiation ◽  
Fibroblast Growth ◽  
Brain Areas

Procurement of multipotential neuroglial stem cells is possible with the addition of epidermal growth factor (EGF). Stem cells will differentiate into neurons and glia upon the removal of EGF from the culture medium. We have previously characterized the neuronal differentiation of stem cells derived from long-term cultured nonpassage neurospheres. In the current study, we (1) characterize the morphological differentiation of the astroglial progenitor cell from 3-mo-old neurospheres, (2) examine whether the astroglial progenitor cells from neurospheres of different brain areas exhibit different differentiation responses to the same exogenous signals, and (3) test the effects of basic fibroblast growth factor (bFGF) and retinol on differentiation. Cerebral cortex, striatum, and mesencephalon cells were obtained from Embryonic Day 14 (E-14) rat fetuses and were dissociated for the procurement of neurospheres in chemically defined medium supplemented with EGF. After 3 mo in culture, the neurospheres, derived from each of the three brain areas, were subcultured into three groups on chamber slides: (1) basal medium, (2) the basal medium plus 20 ng/mL bFGF, and (3) the basal medium plus 10 μM retinol. Phenotypic expression of astroglial cells was examined after 14 days subculture. Our findings indicate that the 3-mo-old cultured nonpassage neurospheres contained numerous multipotential stem cells that stained positive with nestin, and that environmental factors played an important role in influencing the differentiation of astroglial progenitor cells. As detected by glial fibrillary acid protein (GFAP), astroglial progenitor cells turned into protoplasmic astrocytes in the FCS-containing basal medium, fibrous astrocytes in the presence of bFGF, and spindle-shaped astrocytes in the presence of retinol. There were no noticeable differences in differentiation among astroglial progenitor cells of the various brain region-derived neurospheres in any of the three medium conditions. Peculiar varicosity-and growth cone-like structures on the long slender GFAP-positive processes suggest that neuroblasts and glioblast may share common morphologies, features, or common progenitor cells during initial differentiation in vitro.

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