Focal segmental glomerulosclerosis (FSGS) is a frequent and severe glomerular disease characterized by destabilization of podocyte foot processes. We report that transgenic expression of the microRNA miR-193a in mice rapidly induces FSGS with extensive podocyte foot process effacement. Mechanistically, miR-193a inhibits the expression of the Wilms' tumor protein (WT1), a transcription factor and master regulator of podocyte differentiation and homeostasis. Decreased expression levels of WT1 lead to downregulation of its target genes PODXL (podocalyxin) and NPHS1 (nephrin), as well as several other genes crucial for the architecture of podocytes, initiating a catastrophic collapse of the entire podocyte-stabilizing system. We found upregulation of miR-193a in isolated glomeruli from individuals with FSGS compared to normal kidneys or individuals with other glomerular diseases. Thus, upregulation of miR-193a provides a new pathogenic mechanism for FSGS and is a potential therapeutic target.
Solar vapor generation has attracted
tremendous attention as one
of the most efficient ways of utilizing solar energy. It is highly
desirable to develop low-cost, eco-friendly, and high-efficiency solar
absorbers for practical applications of solar vapor generation. Herein,
a three-dimensional plasmonic covellite CuS hierarchical nanostructure
has been synthesized as the light-absorbing material via a facile
one-pot hydrothermal method for structurally integrated solar absorbers
with microporous poly(vinylidene fluoride) membrane (PVDFM) as the
supporting material. A broadband and highly efficient light absorption
has been achieved in the wavelength of 300–2500 nm, along with
high water evaporation efficiencies of 90.4 ± 1.1 and 93.3 ±
2.0% under 1 and 4 sun irradiation, respectively. Meanwhile, stable
performance has been demonstrated for over 20 consecutive runs without
much performance degradation. To the best of our knowledge, this is
the highest performance among the copper sulfide-based solar absorbers.
With the additional features of low-cost and convenient fabrication,
this plasmonic solar absorber exhibits a tremendous potential for
practical solar vapor generation.
The increased proliferation and migration of vascular smooth muscle cells (VSMCs) are key events in the development of atherosclerotic lesions. Baicalin, an herb-derived flavonoid compound, has been previously shown to induce apoptosis and growth inhibition in cancer cells through multiple pathways. However, the potential role of baicalin in regulation of VSMC proliferation and prevention of cardiovascular diseases remains unexplored. In this study, we show that pretreatment with baicalin has a dose-dependent inhibitory effect on PDGF-BB-stimulated VSMC proliferation, accompanied with the reduction of proliferating cell nuclear antigen (PCNA) expression. We also show that baicalin-induced growth inhibition is associated with a decrease in cyclin E-CDK2 activation and increase in p27 level in PDGF-stimulated VSMCs, which appears to be at least partly mediated by blockade of PDGF receptor β (PDGFRβ)-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. In addition, baicalin was also found to inhibit adhesion molecule expression and cell migration induced by PDGF-BB in VSMCs. Furthermore, using an animal carotid arterial balloon-injury model, we found that baicalin significantly inhibited neointimal hyperplasia. Taken together, our results reveal a novel function of baicalin in inducing growth arrest of PDGF-stimulated VSMCs and suppressing neointimal hyperplasia after balloon injury, and suggest that the underlying mechanism involves the inhibition of cyclin E-CDK2 activation and the increase in p27 accumulation via blockade of the PDGFRβ-ERK1/2 signaling cascade.
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