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Epidermal growth factor receptor (EGFR) has been implicated in the pathogenesis of diabetic nephropathy and renal fibrosis; however, the causative role of sustained EGFR activation is unclear. Here, we generated a novel kidney fibrotic mouse model of persistent EGFR activation by selectively expressing the EGFR ligand, human heparin-binding EGF-like growth factor (hHB-EGF), in renal proximal tubule epithelium. hHB-EGF expression increased tyrosine kinase phosphorylation of EGFR and the subsequent activation of downstream signaling pathways, including ERK and AKT, as well as the profibrotic TGF-β1/SMAD pathway. Epithelial-specific activation of EGFR was sufficient to promote spontaneous and progressive renal tubulointerstitial fibrosis, as characterized by increased collagen deposition, immune cell infiltration, and α-smooth muscle actin (α-SMA)-positive myofibroblasts. Tubule-specific EGFR activation promoted epithelial dedifferentiation and cell-cycle arrest. Furthermore, EGFR activation in epithelial cells promoted the proliferation of α-SMA+ myofibroblasts in a paracrine manner. Genetic or pharmacologic inhibition of EGFR tyrosine kinase activity or downstream MEK activity attenuated the fibrotic phenotype. This study provides definitive evidence that sustained activation of EGFR in proximal epithelia is sufficient to cause spontaneous, progressive renal tubulointerstitial fibrosis, evident by epithelial dedifferentiation, increased myofibroblasts, immune cell infiltration, and increased matrix deposition. [ABSTRACT FROM AUTHOR]

Two distributed consensus problems, including leadless consensus and tracking consensus, for multiple quadrotors with bounded disturbances under a directed topology are solved in this study. First, the model of a single quadrotor is divided into two subsystems. Some coupling terms between the two subsystems are regarded as external perturbations. For the case of leadless consensus, a distributed sliding-mode controller for the first subsystem and a state-feedback controller for the second subsystem are proposed to guarantee that the consensus is achieved with bounded errors that are only associated with disturbances. For the case of tracking consensus, by using the proposed sliding-mode consensus protocols combining with two sliding-mode observers, it is shown that all quadrotors can track the leader with bounded errors which can be manipulated suitably. Simulations show the effectiveness of the proposed control protocols. [ABSTRACT FROM AUTHOR]