22 research outputs found
Antiangiogenic small molecule ligands of FGF2 derived from the endogenous inhibitor thrombospondin-1
Thrombospondin-1 protects against Aβ-induced mitochondrial fragmentation and dysfunction in hippocampal cells
TNFÎą induces inflammatory stress response in microvascular endothelial cells via Akt- and P38 MAP kinase-mediated thrombospondin-1 expression
Alteration in cellular turnover and progenitor cell population in lacrimal glands from thrombospondin 1 â/â mice, a model of dry eye
Predictive model of thrombospondin-1 and vascular endothelial growth factor in breast tumor tissue
Identification of plasma protein markers common to patients with malignant tumour and Abnormal Savda in Uighur medicine: a prospective clinical study
Thrombospondin 1 protects pancreatic β-cells from lipotoxicity via the PERK-NRF2 pathway
The failure of β-cells has a central role in the pathogenesis of type 2 diabetes, and the identification of novel approaches to improve functional β-cell mass is essential to prevent/revert the disease. Here we show a critical novel role for thrombospondin 1 (THBS1) in β-cell survival during lipotoxic stress in rat, mouse and human models. THBS1 acts from within the endoplasmic reticulum to activate PERK and NRF2 and induce a protective antioxidant defense response against palmitate. Prolonged palmitate exposure causes THBS1 degradation, oxidative stress, activation of JNK and upregulation of PUMA, culminating in β-cell death. These findings shed light on the mechanisms leading to β-cell failure during metabolic stress and point to THBS1 as an interesting therapeutic target to prevent oxidative stress in type 2 diabetes