scholarly journals The Role of Transforming Growth Factor-Beta in Retinal Ganglion Cells with Hyperglycemia and Oxidative Stress

2020 ◽  
Vol 21 (18) ◽  
pp. 6482
Author(s):  
Hsin-Yi Chen ◽  
Yi-Jung Ho ◽  
Hsiu-Chuan Chou ◽  
En-Chi Liao ◽  
Yi-Ting Tsai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Retinal Ganglion Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Ganglion Cells ◽  
Heme Oxygenase 1 ◽  
Retinal Ganglion ◽  
Growth Factor Beta

A characteristic of diabetes mellitus is hyperglycemia, which is considered with an emphasis on the diabetic retinopathy of progressive neurodegenerative disease. Retinal ganglion cells (RGCs) are believed to be important cells affected in the pathogenesis of diabetic retinopathy. Transforming growth factor-beta (TGF-β) is a neuroprotective protein that helps to withstand various neuronal injuries. To investigate the potential roles and regulatory mechanisms of TGF-β in hyperglycemia-triggered damage of RGCs in vitro, we established RGCs in 5.5, 25, 50, and 100 mM D-glucose supplemented media and focused on the TGF-β-related oxidative stress pathway in combination with hydrogen peroxide (H2O2). Functional experiments showed that TGF-β1/2 protein expression was upregulated in RGCs with hyperglycemia. The knockdown of TGF-β enhanced the accumulation of reactive oxygen species (ROS), inhibited the cell proliferation rate, and reduced glutathione content in hyperglycemia. Furthermore, the results showed that the TGF-β-mediated enhancement of antioxidant signaling was correlated with the activation of stress response proteins and the antioxidant pathway, such as aldehyde dehydrogenase 3A1 (ALDH3A1), heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor (Nrf2), and hypoxia-inducible factor (HIF-1α). Summarizing, our results demonstrated that TGF-β keeps RGCs from hyperglycemia-triggered harm by promoting the activation of the antioxidant pathway, suggesting a potential anti-diabetic therapy for the treatment of diabetic retinopathy.

scholarly journals Serum Concentrations of Transforming Growth Factor-Beta 1 in Predicting the Occurrence of Diabetic Retinopathy in Juvenile Patients with Type 1 Diabetes Mellitus

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Katarzyna Zorena ◽  
Ewa Malinowska ◽  
Dorota Raczyńska ◽  
Małgorzata Myśliwiec ◽  
Krystyna Raczyńska
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Type 1 Diabetes Mellitus ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Serum Concentrations ◽  
Growth Factor Beta

In the present study, we have decided to evaluate if serum transforming growth factor-beta 1 (TGF-β1) concentrations may have diagnostic value in predicting the occurrence of diabetic retinopathy (DR) in juvenile patients with type 1 diabetes mellitus (T1DM). The study included 81 children and adolescents with T1DM and 19 control subjects. All study participants had biochemical parameters examined, underwent an eye examination, and 24-hour blood pressure monitoring. Moreover, serum concentrations of TGF-β1 were measured. The group of patients with T1DM and nonproliferative diabetic retinopathy (NPDR) had statistically significant higher serum levels of TGF-β1 (P=0.001) as compared to T1DM patients without retinopathy as well as the healthy control subject. The threshold serum TGF-β1 concentrations which had a discriminative ability to predict the presence of DR were calculated using the receiver operating characteristic (ROC) curves analysis and amounted to 443 pg/ml. The area under the ROC curve (AUCROC) was 0.80, and its population value was in the range of 0.66 to 0.94. The sensitivity and specificity were calculated to be 72% and 88%, respectively. Our results suggest that TGF-β1 serum concentrations may be an additional parameter in predicting the occurrence of DR in juvenile patients with T1DM.

scholarly journals Correlation between Oxidative Stress and Transforming Growth Factor-Beta in Cancers

2021 ◽  
Vol 22 (24) ◽  
pp. 13181
Author(s):  
Jinwook Chung ◽  
Md Nazmul Huda ◽  
Yoonhwa Shin ◽  
Sunhee Han ◽  
Salima Akter ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Factor ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Transforming Growth Factor Beta ◽  
Cancer Biology ◽  
Cancer Metastasis ◽  
Transforming Growth Factor ◽  
Antioxidant Systems ◽  
Growth Factor Beta

The downregulation of reactive oxygen species (ROS) facilitates precancerous tumor development, even though increasing the level of ROS can promote metastasis. The transforming growth factor-beta (TGF-β) signaling pathway plays an anti-tumorigenic role in the initial stages of cancer development but a pro-tumorigenic role in later stages that fosters cancer metastasis. TGF-β can regulate the production of ROS unambiguously or downregulate antioxidant systems. ROS can influence TGF-β signaling by enhancing its expression and activation. Thus, TGF-β signaling and ROS might significantly coordinate cellular processes that cancer cells employ to expedite their malignancy. In cancer cells, interplay between oxidative stress and TGF-β is critical for tumorigenesis and cancer progression. Thus, both TGF-β and ROS can develop a robust relationship in cancer cells to augment their malignancy. This review focuses on the appropriate interpretation of this crosstalk between TGF-β and oxidative stress in cancer, exposing new potential approaches in cancer biology.

Thrombospondin-1 (TSP1), Transforming Growth Factor-Beta (TGFb) and Connective Tissue Growth Factor (CTGF) are Involved in the Pathophysiology of Diabetic Retinopathy,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3275-3275
Author(s):  
Raul A. De La Cadena ◽  
Mario C Rico ◽  
Fabiola Del Carpio-Cano ◽  
Fayez Safadi ◽  
Satya P. Kunapuli ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Western Blotting ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Control Groups ◽  
Vitreous Fluid ◽  
Growth Factor Beta

Abstract Abstract 3275 Background: Diabetic retinopathy (DR) is a progressive disease that affects over 4 million people in the United States and is one of the leading causes of blindness. The pathophysiology of the early events (no evidence of DR) leading to diabetic retinopathy is still not fully understood. Recent studies have proposed that levels of TSP1 (Arch Ophthalmol 127:507, 2009) and CTGF (Diabetes Care 27:758, 2004) may play a role in shifting the angiogenic balance and pathogenesis of DR. We postulate that during acute and chronic inflammation, as seen in type-2 diabetes a pro-inflammatory axis comprised by TSP1, transforming growth factor-beta (TGF-b) and CTGF may play a significant role in the progression of NPDR to PDR. Methods: This is a prospective control study comprised to date of: a) six (6) human subjects with NPDR, b) eleven (11) subjects with PDR, c) five (5) subjects without type-2 diabetes but in need of pars plana vitrectomy, and d) seventeen (17) normal human volunteers. Plasma samples were obtained from all groups (a-d) after signing an informed consent approved by our institution's IRB committee. Vitreous fluid (VF) was collected from subjects in b and c. Cytokine profile was determined by Multiplex Assay. TSP1, TGF-b and CTGF were assessed by commercially available ELISA assays and visualized by Western-blotting technique. Results: TNFa in conjunction with other pro-inflammatory cytokines was found elevated in NPDR subjects when compared to subjects in control groups (c-d, P<0.05). The evidence of acute inflammation in the NPDR group was not only evident by higher levels of TNFa but also TSP1 and TGF-b when compared to control groups (P<0.002 and P<0.001 respectively). Interestingly, the TSP1 profile seen in the NPDR subjects changed significantly (lower levels) when compared to PDR subjects (P<0.002) and was even significantly different from that one seen in control subjects. This early foot print observed for TSP1 was similar to the IL-4 profile (P<0.003 NPDR vs PDR, P<0.0002 NPDR vs controls) a molecule considered to be anti-angiogenic like TSP1. CTGF plasma levels were increased in PDR subjects in plasma (mean 1.67 + 0.27 SEM pg/ml) when compared to NPDR subjects (0.77 + 0.22 pg/ml, P<0.05) and the levels were also higher in VH of PDR subjects when compared with VH controls subjects. On Western-blotting analysis, CTGF and TSP1 in plasma and in VH showed evidence of proteolytic fragmentation, a phenomenon that has been associated with potential promotion of angiogenesis and fibrosis. Summary: Our findings are in agreement with the proposed hypothesis that TSP1 in systemic circulation or in the micro environment (vitreous fluid) in conjunction with TGF-b represent a pro-inflammatory axis in the disease progression from NPDR to PDR with CTGF as the effector molecule placing this axis as a potential therapeutic intervention to prevent progression of disease and to improve quality of life in patients afflicted by NPDR. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The TGFβ1 Receptor Antagonist GW788388 Reduces JNK Activation and Protects Against Acetaminophen Hepatotoxicity in Mice

2019 ◽  
Vol 170 (2) ◽  
pp. 549-561 ◽  
Author(s):  
Matthew McMillin ◽  
Stephanie Grant ◽  
Gabriel Frampton ◽  
Anca D Petrescu ◽  
Elaina Williams ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Growth Factor ◽  
Liver Injury ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Necrotic Cell Death ◽  
Necrotic Cell ◽  
Growth Factor Beta ◽  
And Oxidative Stress

Abstract Acute liver failure is a serious consequence of acetaminophen (APAP)-induced hepatotoxic liver injury with high rates of morbidity and mortality. Transforming growth factor beta 1 (TGFβ1) is elevated during liver injury and influences hepatocyte senescence during APAP-induced hepatotoxicity. This study investigated TGFβ1 signaling in the context of inflammation, necrotic cell death, and oxidative stress during APAP-induced liver injury. Male C57Bl/6 mice were injected with 600 mg/kg APAP to generate liver injury in the presence or absence of the TGFβ receptor 1 inhibitor, GW788388, 1 h prior to APAP administration. Acetaminophen-induced liver injury was characterized using histological and biochemical measures. Transforming growth factor beta 1 expression and signal transduction were assessed using immunohistochemistry, Western blotting and ELISA assays. Hepatic necrosis, liver injury, cell proliferation, hepatic inflammation, and oxidative stress were assessed in all mice. Acetaminophen administration significantly induced necrosis and elevated serum transaminases compared with control mice. Transforming growth factor beta 1 staining was observed in and around areas of necrosis with phosphorylation of SMAD3 observed in hepatocytes neighboring necrotic areas in APAP-treated mice. Pretreatment with GW788388 prior to APAP administration in mice reduced hepatocyte cell death and stimulated regeneration. Phosphorylation of SMAD3 was reduced in APAP mice pretreated with GW788388 and this correlated with reduced hepatic cytokine production and oxidative stress. These results support that TGFβ1 signaling plays a significant role in APAP-induced liver injury by influencing necrotic cell death, inflammation, oxidative stress, and hepatocyte regeneration. In conclusion, targeting TGFβ1 or downstream signaling may be a possible therapeutic target for the management of APAP-induced liver injury.

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