Transforming growth factor-β1 (TGF-β1) plays an important role on fibrogenesis in heart disease. MicroRNAs have exhibited as crucial regulators of cardiac homeostasis and remodeling in various heart diseases. MiR-19a-3p/19b-3p expresses with low levels in the plasma of heart failure patients. The purpose of our study is to determine the role of MiR-19a-3p/19b-3p in regulating autophagy-mediated fibrosis of human cardiac fibroblasts. We elucidate our hypothesis in clinical samples and human cardiac fibroblasts (HCF) to provide valuable basic information. TGF-β1 promotes collagen I α2 and fibronectin synthesis in HCF and that is paralleled by autophagic activation in these cells. Pharmacological inhibition of autophagy by 3-methyladenine decreases the fibrotic response, while autophagy induction of rapamycin increases the response. BECN1 knockdown and Atg5 over-expression either inhibits or enhances the fibrotic effect of TGF-β1 in experimental HCF. Furthermore, miR-19a-3p/19b-3p mimics inhibit epithelial mesenchymal transition (EMT) and extracellular matrix (ECM) prodution and invasion of HCF. Functional studies suggest that miR-19a-3p/19b-3p inhibits autophagy of HCF through targeting TGF-β R II mRNA. Moreover, enhancement of autophagy rescues inhibition effect of miR-19a-3p/19b-3p on Smad 2 and Akt phosphorylation through TGF-β R II signaling. Our study uncovers a novel mechanism that miR-19a-3p/19b-3p inhibits autophagy-mediated fibrogenesis by targeting TGF-β R II.

AEG-1/MTDH-activated autophagy enhances human malignant glioma susceptibility to TGF-β1-triggered epithelial-mesenchymal transition AEG-1/MTDH-activated autophagy enhances human malignant glioma susceptibility to TGF-β1-triggered epithelial-mesenchymal transition

Somatostatin-secreting δ-cells have aroused great attention due to their powerful roles in coordination of islet insulin and glucagon secretion and maintenance of glucose homeostasis. δ-cells exhibit neuron-like morphology with projections which enable pan-islet somatostatin paracrine regulation despite their scarcity in the islets. The expression of a range of hormone and neurotransmitter receptors allows δ-cells to integrate paracrine, endocrine, neural and nutritional inputs, and provide rapid and precise feedback modulations on glucagon and insulin secretion from α- and β-cells, respectively. Interestingly, the paracrine tone of δ-cells can be effectively modified in response to factors released by neighboring cells in this interactive communication, such as insulin, urocortin 3 and γ-aminobutyric acid from β-cells, glucagon, glutamate and glucagon-like peptide-1 from α-cells. In the setting of diabetes, defects in δ-cell function lead to suboptimal insulin and glucagon outputs and lift the glycemic set-point. The interaction of δ-cells and non-δ-cells also becomes defective in diabetes, with reduces paracrine feedback to β-cells to exacerbate hyperglycemia or enhanced inhibition of α-cells, disabling counter-regulation, to cause hypoglycemia. Thus, it is possible to restore/optimize islet function in diabetes targeting somatostatin signaling, which could open novel avenues for the development of effective diabetic treatments.