Images under the category fibrosis
- Figure 8Overview of the signalling pathways of H2R activation influencing HF Pressure overload increases myocardial density of mast cells and promotes histamine production and up-regulation of H2R. Activation of H2R by histamine exerts distinct roles on fibroblasts and cardiomyocytes. In fibroblasts, H2R activation stimulates the pathway of calcineurin/nuclear translocation of NFAT/fibronectin/procollagen/cell proliferation/fibrosis, whereas in cardiomyocytes, H2R activation stimulates the pathway of mitochondrial translocation of Bax/mitochondrial permeability increase/cleavage caspase-3/apoptosis. Both fibrosis and cardiomyocyte apoptosis promote the progression of HF. αq, Gq-protein α subunit; PLC, phospholipase C; PLP2, phosphatidylinositol 4,5-bisphosphate; IP3, inositol trisphosphate; CaM, calmodulin; αs, Gs-protein α subunit.
- Figure 1A simplified schematic diagram representing TLR2 and TLR4 signalling in the diabetic kidney The release of endogenous ligands in the diabetic milieu (hyperglycaemia, dyslipidaemia and hypoxia) activates TLR2 and TLR4 in immune and kidney cells. Activation of TLR2 initiates the MyD88-dependent pathway, whereas TLR4 engagement initiates MyD88-dependent and MyD88-independent signalling pathways. However, the pathways converge in the activation of NF-κB, which is responsible for the synthesis and secretion of pro-inflammatory cytokines, chemokines, cell adhesion molecules and pro-fibrotic markers involved in inflammation and fibrosis, eventually leading to diabetic nephropathy.
- Figure 2Therapeutic targets of TGF-β1/BMP7/Smad signalling for kidney disease (i) Administration of BMP7 attenuates renal inflammation and fibrosis. (ii) Inhibition of BMP antagonists, such as USAG-1, Gremlin, Chordin-like1, Crim1 and Kielin/Chordin-like protein (KCP), protects against renal injury; (iii) THR-123, a small-peptide agonist of BMP signalling which functions through the Alk3 receptor to inhibit renal inflammation and fibrosis. (iv) Overexpression of Smad7 suppresses NF-κB-driven renal inflammation and TGF-β/Smad3-mediated fibrosis. (v) Alteration of TGF-β/BMP-7/Smad-regulated microRNAs, such as inhibition of miR-21 and miR-192, while up-regulating miR-29 and miR-200, suppresses renal fibrosis. BMPRI etc., BMPR type I etc.; KD, knockdown; OVE, overexpression; p, phosphorylation.