Ablation of the N-type calcium channel ameliorates diabetic nephropathy with improved glycemic control and reduced blood pressure

Pharmacological blockade of the N-and L-type calcium channel lessens renal injury in kidney disease patients. The significance of specific blockade of α1 subunit of N-type calcium channel, Cav2.2, in diabetic nephropathy, however, remains to be clarified. To examine functional roles, we mated Cav2.2-/- mice with db/db (diabetic) mice on the C57BLKS background. Cav2.2 was localized in glomeruli including podocytes and in distal tubular cells. Diabetic Cav2.2-/- mice significantly reduced urinary albumin excretion, glomerular hyperfiltration, blood glucose levels, histological deterioration and systolic blood pressure (SBP) with decreased urinary catecholamine compared to diabetic Cav2.2+/+ mice. Interestingly, diabetic heterozygous Cav2.2+/- mice also decreased albuminuria, although they exhibited comparable systolic blood pressure, sympathetic nerve activity and creatinine clearance to diabetic Cav2.2+/+ mice. Consistently, diabetic mice with cilnidipine, an N-/L-type calcium channel blocker, showed a reduction in albuminuria and improvement of glomerular changes compared to diabetic mice with nitrendipine. In cultured podocytes, depolarization-dependent calcium responses were decreased by Ω-conotoxin, a Cav2.2-specific inhibitor. Furthermore, reduction of nephrin by transforming growth factor-β (TGF-β) in podocytes was abolished with Ω-conotoxin, cilnidipine or mitogen-activated protein kinase kinase inhibitor. In conclusion, Cav2.2 inhibition exerts renoprotective effects against the progression of diabetic nephropathy, partly by protecting podocytes.</p

Growth kinetics and theoretical modeling of selective molecular beam epitaxy for growth of GaAs nanowires on nonplanar (001) and (111)B substrates

The growth kinetics involved in the selective molecular beam epitaxy growth of GaAs quantum wires (QWRs) on mesa-patterned substrates is investigated in detail experimentally, and an attempt is made to model the growth theoretically, using a phenomenological continuum model. Experimentally, -oriented QWRs were grown on (001) and (113)A substrates, and -oriented QWRs were grown on (111)B substrates. From a detailed investigation of the growth profiles, it was found that the lateral wire width is determined by facet boundaries (FBs) within AlGaAs layers separating growth regions on top facets from those on side facets of mesa structures. Evolution of FBs during growth was complicated. For computer simulation, measured growth rates of various facets were fitted into a theoretical formula to determine the dependence of a lifetime of adatoms on the slope angle of the growing surface. The continuum model using the slope angle dependent lifetime reproduced the details of the experimentally observed growth profiles very well for growth on (001), (113)A, and (111)B substrates, including the complex evolution of facet boundarie

Selective molecular beam epitaxy growth of size- and position-controlled GaN/AlGaN nanowires on nonplanar (0001) substrates and its growth mechanism

Fundamental growth properties were investigated for the size-controlled selective MBE growth of AlGaN/GaN nanowires on the GaN (0001) prepatterned substrates both experimentally and theoretically. The lateral size of the present GaN nanowire was determined by two facet boundaries formed within AlGaN barrier layers. From the series of wire growth experiments, the growth selectivity and the measured angle of the facet boundary strongly depended on the Al composition and the initial crystalline facets of the mesa patterned templates. The experimental evolution of the cross-sectional structures was well reproduced by a computer simulation based on the phenomenological growth model where the slope angle dependence of lifetime of adatoms was taken into account. The lateral width of present nanowires could be kinetically controlled by the growth conditions and the supply thickness of AlGaN layers

Growth kinetics and modeling of selective molecular beam epitaxial growth of GaAs ridge quantum wires on pre-patterned nonplanar substrates

The growth kinetics involved in the selective molecular beam epitaxial growth of GaAs ridge QWRs is investigated in detail experimentally and an attempt is made to model the growth theoretically. For this purpose, detailed experiments were carried out on the growth of -oriented AlGaAs-GaAs ridge quantum wires on mesa-patterned (001) GaAs substrates.Aphenomenological modeling was done based on the continuum approximation including parameters such as group III adatom lifetime, diffusion constant and migration length. Computer simulation using the resultant model well reproduces the experimentally observed growth features such as the cross-sectional structure of the ridge wire and its temporal evolution, its temperature dependence and evolution of facet boundary planes. The simple phenomenological model developed here seems to be very useful for design and precise control of the growth process