neutralizing antibody against tgfβ 1–3 clone 1d11  (Genzyme)

Journal: Biomolecules

Article Title: TGFβ-Neurotrophin Interactions in Heart, Retina, and Brain

doi: 10.3390/biom11091360

Figure Lengend Snippet: Neurotrophin and TGFβ signaling. ( A ) Simplified scheme showing neurotrophin and Smad-dependent TGFβ signaling pathways. ( B ) Quantitative real time RT-PCR (qPCR) of Ngf mRNA expression in Tgfbr2 Δoc and Smad7 Δoc -deficient and in their respective control littermate’s retinae. Data are mean ± SEM, n ≥ 5, * p = 0.0214 ( Tgfbr2 Δoc ), * p = 0.0366 ( Smad7 Δoc ). Expression is normalized to Gapdh. ( C ) QPCR analyses of RNA samples from neuronal cells (RGC-5 cells) treated with TGFβ2 (1 and 3 ng) or in combination with SIS3 (1 µM + 3 ng TGFβ2), an inhibitor of Smad3 phosphorylation. Ngf mRNA expression significantly increases following TGFβ treatment and its expression reverses to control levels if TGFβ is inhibited. Data are mean ± SEM, n ≥ 4, * p = 0.0119 (3 ng TGFβ2), ** p = 0.0059 (SIS3 + TGFβ2). Expression is normalized to Gapdh . ( D ) NGF immunoreactivity (red) in the retinae of Tgfbr2 Δoc , control and Smad7 Δoc -deficient mice at postnatal day 10. Nuclei are DAPI stained (blue). In the retina of the Smad7 Δoc -deficient mouse, NGF immunoreactivity is considerably stronger with distinct preference for the perikarya (arrowheads) in the ganglion cell, inner nuclear and outer plexiform layer. In contrast labeling of the perikarya in the ganglion cell, inner nuclear and outer plexiform layer is less frequent and intense in the control retina and rarely observed in the Tgfbr2 Δoc retina. The original data from ( B – D ), that we show in a slightly modified representation here, have been published in . NGF = nerve growth factor, BDNF = brain-derived neurotrophic factor, NT-3 = neurotrophin 3, proNT = pro Neurotrophin, mNT = mature neurotrophin, TGFβ = transforming growth factor β, Trk A–C = tropomyosin receptor kinase A–C, p75 = p75 neurotrophin receptor, TGFβRI/II = transforming growth factor beta receptor 1/2, PLC y = phospholipase C gamma, PKC = protein kinase C, MAPK = mitogen-activated protein kinase, TFs = transcription factors, PI3-K = phosphoinositide 3-kinase, NF-kB = nuclear factor kappa-light-chain-enhancer of activated B cells, JNK = c-Jun N-terminal kinase, GCL = ganglion cell layer, INL = inner nuclear layer, ONL = outer nuclear layer.

Article Snippet: Systemic inhibition of TGFβ signaling by administering a neutralizing antibody against TGFβ 1–3 (clone 1D11, Genzyme) starting on day one of experimentally induced MI (and 3 x/week thereafter) confirmed the detrimental effects of systemic TGFβ inhibition as all anti-TGFβ-treated animals died within 5 days, whereas control antibody-treated mice showed the expected 40% mortality rate [ ].

Techniques: Protein-Protein interactions, Quantitative RT-PCR, Expressing, Control, Phospho-proteomics, Staining, Labeling, Modification, Derivative Assay

Journal: Biomolecules

Article Title: TGFβ-Neurotrophin Interactions in Heart, Retina, and Brain

doi: 10.3390/biom11091360

Figure Lengend Snippet: Neurotrophin and TGFβ signaling in myocardial infarction (MI). Scheme illustrating the three phases following MI that comprise the inflammatory, proliferative, and maturation phase. During each phase, multiple cellular processes occur, with the ultimate goal of healing the affected tissue. Neurotrophins and TGFβ are upregulated following MI and modulate processes in the inflammatory, proliferative, and maturation phase. TGFβ = transforming growth factor β, NT = neurotrophins.

Article Snippet: Systemic inhibition of TGFβ signaling by administering a neutralizing antibody against TGFβ 1–3 (clone 1D11, Genzyme) starting on day one of experimentally induced MI (and 3 x/week thereafter) confirmed the detrimental effects of systemic TGFβ inhibition as all anti-TGFβ-treated animals died within 5 days, whereas control antibody-treated mice showed the expected 40% mortality rate [ ].

Techniques:

Journal: Biomolecules

Article Title: TGFβ-Neurotrophin Interactions in Heart, Retina, and Brain

doi: 10.3390/biom11091360

Figure Lengend Snippet: Angiogenic properties of neurotrophin and TGFβ signaling. Scheme showing the interplay of neurotrophins, TGFβ signaling, and endothelial cells in the retina. TGFβ mediates upregulation of neurotrophins in the retina, which promote angiogenesis either by direct binding to Trk receptors on endothelial cells, or by inducing VEGF expression and subsequent activation of VEGFR2. TGFβ = transforming growth factor β, VEGF = vascular endothelial growth factor, VEGFR2 = vascular endothelial growth factor receptor 2, Trk = tropomyosin receptor kinase.

Article Snippet: Systemic inhibition of TGFβ signaling by administering a neutralizing antibody against TGFβ 1–3 (clone 1D11, Genzyme) starting on day one of experimentally induced MI (and 3 x/week thereafter) confirmed the detrimental effects of systemic TGFβ inhibition as all anti-TGFβ-treated animals died within 5 days, whereas control antibody-treated mice showed the expected 40% mortality rate [ ].

Techniques: Binding Assay, Expressing, Activation Assay

Journal: Biomolecules

Article Title: TGFβ-Neurotrophin Interactions in Heart, Retina, and Brain

doi: 10.3390/biom11091360

Figure Lengend Snippet: Deletion of TGFβ signaling results in retinal and choroidal neovascularization. ( A ) Light-sheet fluorescence microscopy of cleared eyes of 6-week-old lectin-injected Tgfbr2 Δeye mice and a control littermate. The control mouse shows an essentially regular arborized retinal vasculature. The Tgfbr2 Δeye mice have an irregular arrangement of the retinal plexus and develop choroidal neovascularization forming anastomoses between retinal and choroidal vessels (arrows). ( B ) FITC-dextran (green) perfused retinal meridional sections of 6-week-old Tgfbr2 ΔEC mice and a control littermate. White arrows point toward tracer leakage in the retinal pigment epithelium (RPE; middle panel) and choroidal neovascularization (right panel) invading the RPE and subretinal space. Nuclei are DAPI stained (blue). ( C ) Meridional section of a 6-week-old FITC-dextran (green) perfused Tgfbr2 Δeye retina shows neovascularization into the vitreous (white arrows), similar to what can be observed in patients suffering from proliferative diabetic retinopathy. Nuclei are DAPI stained (blue). The original data which we show in a slightly modified representation here, have been published in [ , ]. GCL = ganglion cell layer, INL = inner nuclear layer, ONL = outer nuclear layer, RPE = retinal pigment epithelium.

Article Snippet: Systemic inhibition of TGFβ signaling by administering a neutralizing antibody against TGFβ 1–3 (clone 1D11, Genzyme) starting on day one of experimentally induced MI (and 3 x/week thereafter) confirmed the detrimental effects of systemic TGFβ inhibition as all anti-TGFβ-treated animals died within 5 days, whereas control antibody-treated mice showed the expected 40% mortality rate [ ].

Techniques: Fluorescence, Microscopy, Injection, Control, Staining, Modification

Journal: Biomolecules

Article Title: TGFβ-Neurotrophin Interactions in Heart, Retina, and Brain

doi: 10.3390/biom11091360

Figure Lengend Snippet: Roles of TGFβ and neurotrophins in recovery from ischemic stroke. Ischemic stroke is induced by a thrombus occluding a brain artery, which impairs blood supply distal to the occlusion. Neurons within the infarct core (<12 mL blood/100 g tissue/min) die rapidly and become necrotic. Neurons within the penumbra (12–22 mL blood/100 g tissue/min) can recover depending on timely reperfusion and the action of different neuroprotective factors such as TGFβ and neurotrophins. Neurons within the oligemia (22–35 mL blood/100 g tissue/min) usually recover completely from the mild ischemia, irrespective of treatment. Gliosis and neuroinflammation are a response to the tissue damage and regulated by TGFβ and neurotrophins. They can be both beneficial and detrimental to post-stroke recovery and neuronal survival. TGFβ = transforming growth factor β, NGF = nerve growth factor; BDNF = brain-derived neurotrophic factor.

Article Snippet: Systemic inhibition of TGFβ signaling by administering a neutralizing antibody against TGFβ 1–3 (clone 1D11, Genzyme) starting on day one of experimentally induced MI (and 3 x/week thereafter) confirmed the detrimental effects of systemic TGFβ inhibition as all anti-TGFβ-treated animals died within 5 days, whereas control antibody-treated mice showed the expected 40% mortality rate [ ].

Techniques: Derivative Assay

Journal: Biomolecules

Article Title: TGFβ-Neurotrophin Interactions in Heart, Retina, and Brain

doi: 10.3390/biom11091360

Figure Lengend Snippet: The heart-brain and brain-retina axis. Neurotrophins (NT) and TGFβ are upregulated following ischemic insults (red lightning symbol) to the heart, retina, and brain. Following myocardial infarction, the heart-brain axis is activated by transmitting mechano- and chemo-sensitive information through cardiac afferent fibers (dotted arrow) to the brain, which responds by releasing BDNF to the bloodstream. Thus, BDNF promotes recovery from myocardial infarction by endocrine and paracrine actions. TGFβ directly affects repair processes following ischemic insults. Moreover, it has the ability to increase the expression of NT. Additionally, retrograde transport of neurotrophins is essential for survival of retinal ganglion cells. This close relationship could be defined as a brain-retina axis. TGFβ = transforming growth factor β, NT = neurotrophin, BDNF = brain-derived neurotrophic factor.

Article Snippet: Systemic inhibition of TGFβ signaling by administering a neutralizing antibody against TGFβ 1–3 (clone 1D11, Genzyme) starting on day one of experimentally induced MI (and 3 x/week thereafter) confirmed the detrimental effects of systemic TGFβ inhibition as all anti-TGFβ-treated animals died within 5 days, whereas control antibody-treated mice showed the expected 40% mortality rate [ ].

Techniques: Expressing, Derivative Assay