Background: Angiogenesis plays an important role in the survival of tissue, such as blood vessels deliver oxygen and nutrients needed by the cells of the population. Thus, targeting angiogenesis is a prominent strategy in a variety of settings, including both tissue engineering and cancer treatment. However, not all approaches that modulate angiogenesis lead to a successful outcome. angiogenesis based therapies primarily targeting pro-angiogenic factors such as vascular endothelial growth factor-A (VEGF) or fibroblast growth factor (FGF) in isolation, and there is a limited understanding of how these promoters combine together to stimulate angiogenesis. Target one pathway could be enough, because the alternative pathways can compensate, reducing the overall effect of a treatment strategy.
Methods: To gain insight into the mechanistic and identify new therapeutic strategy, we have developed a detailed mathematical models to quantitatively characterize crosstalk of FGF and VEGF intracellular signaling. The model focuses on FGF- and VEGF-induced MAPK (MAPK) signaling to promote cell proliferation and phosphatidylinositol 3-kinase / protein kinase B (PI3K / Akt) pathway, which promotes cell survival and migration. We fit the model for experimental datasets published the size of phosphorylated extracellular regulated kinase (perk) and Akt (pAkt) on FGF or VEGF stimulation. We validate the model with a separate set of data.
Results: We apply mathematical models are trained and validated to characterize the dynamics of Perk and pAkt in response to mono and co-stimulation by FGF and VEGF. The model predicts that for a certain range of ligand concentration, maximum Perk level is more responsive to changes in ligand concentration compared with the maximum level of pAkt. Also, the combination of FGF and VEGF showed a greater effect in increasing the maximum perk than the sum of the individual effects, which are not visible to the maximum pAkt levels. In addition, we identify the model and kinetic parameters affect the species that specifically modulate Perk and pAkt response, which is a potential target for the treatment of angiogenesis-based.
Conclusion: Overall, the model predicts the effect of a combination of FGF and VEGF stimulation on ERK and Akt quantitative and provides a framework for the mechanic to explain experimental results and guide experimental design. Thus, this model can be used to study the effects of the therapy pro- and anti-angiogenic primarily targeting ERK and / or activation of Akt on stimulation with FGF and VEGF. Video Abstract.
ERK and Akt exhibit distinct signaling responses following stimulation by pro-angiogenic factors
TGF-β3 Pressing melanogenesis in cultured human melanocytes with neighboring cells and UV-irradiated human skin
Background: Ultraviolet radiation (UVR) is the most well-known causes of skin pigmentation is accompanied with photoaging. Transforming growth factor (TGF) -β1 shown previously have anti-melanogenic property; However, it can cause scarring in the skin. Objective: We investigated the effect of TGF-β3 on melanogenesis in cultured human melanocytes in the skin constituent cells UV-irradiated and UV-irradiated human skin.
Methods: UVB radiation or treatment with stem cell factor (SCF) and endothelin-1 (ET-1) was applied to human melanocytes cocultured with keratinocytes and / or fibroblasts and ex vivo human skin. mechanistic pathways are further explored after treatment with TGF-β3.
Results: While UVB radiation or SCF / ET-1 enhanced melanogenesis, TGF-β3 accumulation effectively inhibits melanin and tyrosinase activity through downregulation of extracellular signal-regulated kinase (ERK) / microphthalmia associated transcription factor (MITF) pathway. TGF-β3 increased expression of keratinocyte differentiation markers.
Description: A polyclonal antibody against FGF13. Recognizes FGF13 from Human, Mouse, Rat. This antibody is Unconjugated. Tested in the following application: WB, ELISA;WB:1/500-1/2000.ELISA:1/5000
Description: A polyclonal antibody against FGF13. Recognizes FGF13 from Human, Rat. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IHC; Recommended dilution: WB:1:200-1:1000, IHC:1:20-1:200
Description: A polyclonal antibody against FGF13. Recognizes FGF13 from Human. This antibody is Unconjugated. Tested in the following application: ELISA, IHC; Recommended dilution: IHC:1:20-1:200
Description: A polyclonal antibody against FGF13. Recognizes FGF13 from Human, Mouse, Rat. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IHC
Description: A polyclonal antibody against FGF13. Recognizes FGF13 from Human, Mouse. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IHC; Recommended dilution: WB:1:1000-1:5000, IHC:1:20-1:200
Description: A polyclonal antibody against FGF13. Recognizes FGF13 from Human. This antibody is Unconjugated. Tested in the following application: ELISA, WB;WB:1:500-1:3000
Description: A polyclonal antibody against FGF13. Recognizes FGF13 from Human. This antibody is Unconjugated. Tested in the following application: ELISA, WB;WB:1:500-1:3000
Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human FGF13 . This antibody is tested and proven to work in the following applications:
Description: The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth, and invasion. This gene is located in a region on chromosome X, which is associated with Borjeson-Forssman-Lehmann syndrome (BFLS), making it a possible candidate gene for familial cases of the BFLS, and for other syndromal and nonspecific forms of X-linked mental retardation mapping to this region. Alternative splicing of this gene at the 5' end results in several transcript variants encoding different isoforms with different N-termini.
Description: The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth, and invasion. This gene is located in a region on chromosome X, which is associated with Borjeson-Forssman-Lehmann syndrome (BFLS), making it a possible candidate gene for familial cases of the BFLS, and for other syndromal and nonspecific forms of X-linked mental retardation mapping to this region. Alternative splicing of this gene at the 5' end results in several transcript variants encoding different isoforms with different N-termini.
Description: The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth, and invasion. This gene is located in a region on chromosome X, which is associated with Borjeson-Forssman-Lehmann syndrome (BFLS), making it a possible candidate gene for familial cases of the BFLS, and for other syndromal and nonspecific forms of X-linked mental retardation mapping to this region. Alternative splicing of this gene at the 5' end results in several transcript variants encoding different isoforms with different N-termini.
Description: The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth, and invasion. This gene is located in a region on chromosome X, which is associated with Borjeson-Forssman-Lehmann syndrome (BFLS), making it a possible candidate gene for familial cases of the BFLS, and for other syndromal and nonspecific forms of X-linked mental retardation mapping to this region. Alternative splicing of this gene at the 5' end results in several transcript variants encoding different isoforms with different N-termini.
Description: The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth, and invasion. This gene is located in a region on chromosome X, which is associated with Borjeson-Forssman-Lehmann syndrome (BFLS), making it a possible candidate gene for familial cases of the BFLS, and for other syndromal and nonspecific forms of X-linked mental retardation mapping to this region. Alternative splicing of this gene at the 5' end results in several transcript variants encoding different isoforms with different N-termini.
Description: The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth, and invasion. This gene is located in a region on chromosome X, which is associated with Borjeson-Forssman-Lehmann syndrome (BFLS), making it a possible candidate gene for familial cases of the BFLS, and for other syndromal and nonspecific forms of X-linked mental retardation mapping to this region. Alternative splicing of this gene at the 5' end results in several transcript variants encoding different isoforms with different N-termini.
Description: The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth, and invasion. This gene is located in a region on chromosome X, which is associated with Borjeson-Forssman-Lehmann syndrome (BFLS), making it a possible candidate gene for familial cases of the BFLS, and for other syndromal and nonspecific forms of X-linked mental retardation mapping to this region. Alternative splicing of this gene at the 5' end results in several transcript variants encoding different isoforms with different N-termini.
Description: The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth, and invasion. This gene is located in a region on chromosome X, which is associated with Borjeson-Forssman-Lehmann syndrome (BFLS), making it a possible candidate gene for familial cases of the BFLS, and for other syndromal and nonspecific forms of X-linked mental retardation mapping to this region. Alternative splicing of this gene at the 5' end results in several transcript variants encoding different isoforms with different N-termini.
Description: The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth, and invasion. This gene is located in a region on chromosome X, which is associated with Borjeson-Forssman-Lehmann syndrome (BFLS), making it a possible candidate gene for familial cases of the BFLS, and for other syndromal and nonspecific forms of X-linked mental retardation mapping to this region. Alternative splicing of this gene at the 5' end results in several transcript variants encoding different isoforms with different N-termini.
Description: The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth, and invasion. This gene is located in a region on chromosome X, which is associated with Borjeson-Forssman-Lehmann syndrome (BFLS), making it a possible candidate gene for familial cases of the BFLS, and for other syndromal and nonspecific forms of X-linked mental retardation mapping to this region. Alternative splicing of this gene at the 5' end results in several transcript variants encoding different isoforms with different N-termini.
Description: The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth, and invasion. This gene is located in a region on chromosome X, which is associated with Borjeson-Forssman-Lehmann syndrome (BFLS), making it a possible candidate gene for familial cases of the BFLS, and for other syndromal and nonspecific forms of X-linked mental retardation mapping to this region. Alternative splicing of this gene at the 5' end results in several transcript variants encoding different isoforms with different N-termini.
Conclusion: TGF-β3 effectively suppressed UVR-induced melanogenesis showed that topical TGF-β3 may be a suitable candidate for the treatment of hyperpigmentation, UV-related disorders.
Felicia
