High and Low Molecular Weight Fibroblast Growth Factor-2 Increase Proliferation of Neonatal Rat Cardiac Myocytes but Have Differential Effects on Binucleation and Nuclear Morphology

1996 ◽  
Vol 78 (1) ◽  
pp. 126-136 ◽  
Author(s):  
Kishore B.S. Pasumarthi ◽  
Elissavet Kardami ◽  
Peter A. Cattini
Keyword(s):  
Molecular Weight ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Neonatal Rat ◽  
Fibroblast Growth Factor 2 ◽  
Nuclear Morphology ◽  
Low Molecular Weight ◽  
Fibroblast Growth ◽  
Neonatal Rat Cardiac Myocytes ◽  
Rat Cardiac Myocytes

scholarly journals Low molecular weight fibroblast growth factor-2 signals via protein kinase C and myofibrillar proteins to protect against postischemic cardiac dysfunction

2013 ◽  
Vol 304 (10) ◽  
pp. H1382-H1396 ◽  
Author(s):  
Janet R. Manning ◽  
Sarah O. Perkins ◽  
Elizabeth A. Sinclair ◽  
Xiaoqian Gao ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Fibroblast Growth Factor ◽  
Cardiac Dysfunction ◽  
Fibroblast Growth Factor 2 ◽  
Low Molecular Weight ◽  
Fibroblast Growth ◽  
Kinase C

Among its many biological roles, fibroblast growth factor-2 (FGF2) acutely protects the heart from dysfunction associated with ischemia/reperfusion (I/R) injury. Our laboratory has demonstrated that this is due to the activity of the low molecular weight (LMW) isoform of FGF2 and that FGF2-mediated cardioprotection relies on the activity of protein kinase C (PKC); however, which PKC isoforms are responsible for LMW FGF2-mediated cardioprotection, and their downstream targets, remain to be elucidated. To identify the PKC pathway(s) that contributes to postischemic cardiac recovery by LMW FGF2, mouse hearts expressing only LMW FGF2 (HMWKO) were bred to mouse hearts not expressing PKCα (PKCαKO) or subjected to a selective PKCε inhibitor (εV1–2) before and during I/R. Hearts only expressing LMW FGF2 showed significantly improved postischemic recovery of cardiac function following I/R ( P < 0.05), which was significantly abrogated in the absence of PKCα ( P < 0.05) or presence of PKCε inhibition ( P < 0.05). Hearts only expressing LMW FGF2 demonstrated differences in actomyosin ATPase activity as well as increases in the phosphorylation of troponin I and T during I/R compared with wild-type hearts; several of these effects were dependent on PKCα activity. This evidence indicates that both PKCα and PKCε play a role in LMW FGF2-mediated protection from cardiac dysfunction and that PKCα signaling to the contractile apparatus is a key step in the mechanism of LMW FGF2-mediated protection against myocardial dysfunction.

scholarly journals Low-molecular-weight fibroblast growth factor-2 — a viable prognostic factor for gastric gastrointestinal stromal tumors

2021 ◽  
Vol 102 (3) ◽  
pp. 313-321
Author(s):  
E G Mikheeva ◽  
A M Aukhadieva ◽  
A G Sabirov ◽  
S V Boichuk
Keyword(s):  
Molecular Weight ◽  
Growth Factor ◽  
Gastrointestinal Stromal Tumor ◽  
Fibroblast Growth Factor ◽  
Gastrointestinal Stromal Tumors ◽  
Stromal Tumor ◽  
Fibroblast Growth Factor 2 ◽  
Low Molecular Weight ◽  
Fibroblast Growth ◽  
Stromal Tumors

Aim. To examine the expression of fibroblast growth factor-2 and its isoforms in gastrointestinal stromal tumors and assess the prognostic value of this marker. Methods. The study included 44 patients with gastric gastrointestinal stromal tumors of the stomach who were prescribed surgical or combined treatment with the targeted drug imatinib (imatinib mesylate). Immunohistochemistry (IHC)-staining and immunoblotting with monoclonal antibodies were used to assess the expression of FGF-2. Statistical analysis for differences in clinical and morphological parameters was performed by using Students, MannWhitneyWilcoxon and Fishers tests. Differences were considered significant at p 0.05. Results. Fibroblast growth factor-2 expression was assessed in tumor tissues in 39 out of 44 analyzed patients. The frequency of fibroblast growth factor-2 expression in the observed patients was 84.6% (33/39). The moderate and strong fibroblast growth factor-2 expression was detected in 21 (53.8%) patients with gastric gastrointestinal stromal tumors. High expression of low-molecular weight (18 kDa) fibroblast growth factor-2 isoform was found in all tumor samples from patients with high-risk gastrointestinal stromal tumor (prognostic group 6) (p=0.039), which indicated the active secretion of this ligand by its signalling pathway in the cancer cells. Patients with high levels of low‐molecular‐weight fibroblast growth factor-2 showed a higher level of Ki-67 proliferative activity (р=0.013) and tumor size (р=0.0017). Patients with increased expression of the low molecular weight isoform of fibroblast growth factor-2 in gastric gastrointestinal stromal tumor had a higher risk of recurrence, as well as larger tumor size and proliferative activity compared with patients without expression of this isoform. The level of fibroblast growth factor-2 expression in tumor samples, determined by immunohistochemistry-staining, increases after initiation of imatinib to based therapy, which may indicate the formation of resistance to this targeted drug and the progression of the disease. Conclusion. The results of the study suggest that FGF-2 might be an independent prognostic marker of gastric gastrointestinal stromal tumor and a viable therapeutic target.

scholarly journals Elimination or neutralization of endogenous high-molecular-weight FGF2 mitigates doxorubicin-induced cardiotoxicity

2019 ◽  
Vol 316 (2) ◽  
pp. H279-H288 ◽  
Author(s):  
Navid Koleini ◽  
Jon-Jon Santiago ◽  
Barbara E. Nickel ◽  
Glen Lester Sequiera ◽  
Jie Wang ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
High Molecular Weight ◽  
Cardiac Response ◽  
Neonatal Rat ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Cardiac Damage

Cardiac fibroblast growth factor 2 (FGF2) exerts multiple paracrine activities related to cardiac response to injury. Endogenous FGF2 is composed of a mixture of 70% high- and 30% low-molecular-weight isoforms (Hi-FGF2 and Lo-FGF2, respectivley); although exogenously added Lo-FGF2 is cardioprotective, the roles of endogenous Hi-FGF2 or Lo-FGF2 have not been well defined. Therefore, we investigated the effect of elimination of Hi-FGF2 expression on susceptibility to acute cardiac damage in vivo caused by an injection of the genotoxic drug doxorubicin (Dox). Mice genetically depleted of endogenous Hi-FGF2 and expressing only Lo-FGF2 [FGF2(Lo) mice] were protected from the Dox-induced decline in ejection fraction displayed by their wild-type FGF2 [FGF2(WT)] mouse counterparts, regardless of sex, as assessed by echocardiography for up to 10 days post-Dox treatment. Because cardiac FGF2 is produced mainly by nonmyocytes, we next addressed potential contribution of fibroblast-produced FGF2 on myocyte vulnerability to Dox. In cocultures of neonatal rat cardiomyocytes (r-cardiomyocytes) with mouse fibroblasts from FGF2(WT) or FGF2(Lo) mice, only the FGF2(Lo)-fibroblast cocultures protected r-cardiomyocytes from Dox-induced mitochondrial and cellular damage. When r-cardiomyocytes were cocultured with or exposed to conditioned medium from human fibroblasts, neutralizing antibodies for human Hi-FGF-2, but not total FGF2, mitigated Dox-induced injury of cardiomyocytes. We conclude that endogenous Hi-FGF2 reduces cardioprotection by endogenous Lo-FGF2. Antibody-based neutralization of endogenous Hi-FGF2 may offer a prophylactic treatment against agents causing acute cardiac damage. NEW & NOTEWORTHY Cardiomyocytes, in vivo and in vitro, were protected from the deleterious effects of the anticancer drug doxorubicin by the genetic elimination or antibody-based neutralization of endogenous paracrine high-molecular-weight fibroblast growth factor 2 isoforms. These findings have a translational potential for mitigating doxorubicin-induced cardiac damage in patients with cancer by an antibody-based treatment.

scholarly journals Low-molecular-weight fibroblast growth factor 2 attenuates hepatic fibrosis by epigenetic down-regulation of Delta-like1

Hepatology ◽  
2015 ◽  
Vol 61 (5) ◽  
pp. 1708-1720 ◽  
Author(s):  
Ruo-Lang Pan ◽  
Li-Xin Xiang ◽  
Ping Wang ◽  
Xiao-Yuan Liu ◽  
Li Nie ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Hepatic Fibrosis ◽  
Fibroblast Growth Factor 2 ◽  
Low Molecular Weight ◽  
Fibroblast Growth ◽  
Down Regulation
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