ABSTRACT
Renal fibrosis (RF) stands as a pivotal pathological process in the advanced stages of chronic kidney disease (CKD), and impeding its progression is paramount for delaying the advancement of CKD. The miR-10 family, inclusive of miR-10a and miR-10b, has been implicated in the development of various fibrotic diseases. Nevertheless, the precise role of miR-10 in the development of RF remains enigmatic. In this study, we utilized both an in vivo model involving unilateral ureteral obstruction (UUO) in mice and an in vitro model employing TGF-ß1 stimulation in HK-2 cells to unravel the mechanism underlying the involvement of miR-10a/b in RF. The findings revealed heightened expression of miR-10a and miR-10b in the kidneys of UUO mice, accompanied by a substantial increase in p-Smad3 and renal fibrosis-related proteins. Conversely, the deletion of these two genes led to a notable reduction in p-Smad3 levels and the alleviation of RF in mouse kidneys. In the in vitro model of TGF-ß1-stimulated HK-2 cells, the co-overexpression of miR-10a and miR-10b fostered the phosphorylation of Smad3 and RF, while the inhibition of miR-10a and miR-10b resulted in a decrease in p-Smad3 levels and RF. Further research revealed that miR-10a and miR-10b, through binding to the 3'UTR region of Vasohibin-1 (VASH-1), suppressed the expression of VASH-1, thereby promoting the elevation of p-Smad3 and exacerbating the progression of RF. The miR-10 family may play a pivotal role in RF.
Subject(s)
Fibrosis , MicroRNAs , Signal Transduction , Smad3 Protein , MicroRNAs/genetics , MicroRNAs/metabolism , Animals , Smad3 Protein/metabolism , Smad3 Protein/genetics , Mice , Humans , Ureteral Obstruction/metabolism , Ureteral Obstruction/pathology , Ureteral Obstruction/genetics , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/genetics , Male , Cell Line , Kidney/metabolism , Kidney/pathology , Disease Models, Animal , Kidney Diseases/metabolism , Kidney Diseases/genetics , Kidney Diseases/pathology , Mice, Inbred C57BL , Cell Adhesion Molecules/metabolism , Cell Adhesion Molecules/genetics , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/genetics , Renal Insufficiency, Chronic/pathologyABSTRACT
Renal fibrosis (RF) is a common reason for renal failure, and epithelial-mesenchymal transition (EMT) is a vital mechanism that promotes the development of RF. It is known that microRNA-10 (miR-10) plays an important role in cancer EMT; however, whether it takes part in the EMT process of RF remains unclear. Therefore, we established an in vivo model of unilateral ureteral obstruction (UUO), and an in vitro model using TGF-ß1, to investigate whether and how miR-10a and miR-10b take part in the EMT of RF. In addition, the combinatorial effects of miR-10a and miR-10b were assessed. We discovered that miR-10a and miR-10b are overexpressed in UUO mice, and miR-10a, miR-10b, and miRs-10a/10b knockout attenuated RF and EMT in UUO-treated mouse kidneys. Moreover, miR-10a and miR-10b overexpression combinatorially promoted RF and EMT in TGF-ß1-treated HK-2 cells. Inhibiting miR-10a and miR-10b attenuated RF and EMT induced by TGF-ß1. Mechanistically, miR-10a and miR-10b suppressed PTEN expression by binding to its mRNA3'-UTR and promoting the Akt pathway. Moreover, PTEN overexpression reduced miR-10a and miR-10b effects on Akt phosphorylation (p-Akt), RF, and EMT in HK-2 cells treated with TGF-ß1. Taken together, miR-10a and miR-10b act combinatorially to negatively regulate PTEN, thereby activating the Akt pathway and promoting the EMT process, which exacerbates RF progression.
ABSTRACT
We report ultra-compact surface-normal high-Q optical filters based on single- and double-layer stacked Fano resonance photonic crystal slabs on both Si and quartz substrates. A single layer photonic crystal filter was designed and a Q factor of 1,737 was obtained with 23 dB extinction ratio. With stacked double-layer photonic crystal configuration, the optical filter Q can increase to over 10,000,000 in design. Double-layer filters with quality factor of 9,734 and extinction ratio of 8 dB were experimentally demonstrated, for a filter design with target Q of 22,000.
ABSTRACT
An aqueous solution-based doping strategy was developed for controlled doping impurity atoms into a ZnO nanowire (NW) lattice. Through this approach, antimony-doped ZnO NWs were successfully synthesized in an aqueous solution containing zinc nitrate and hexamethylenetetramine with antimony acetate as the dopant source. By introducing glycolate ions into the solution, a soluble antimony precursor (antimony glycolate) was formed and a good NW morphology with a controlled antimony doping concentration was successfully achieved. A doping concentration study suggested an antimony glycolate absorption doping mechanism. By fabricating and characterizing NW-based field effect transistors (FETs), stable p-type conductivity was observed. A field effect mobility of 1.2 cm(2) V(-1) s(-1) and a carrier concentration of 6 × 10(17) cm(-3) were achieved. Electrostatic force microscopy (EFM) characterization on doped and undoped ZnO NWs further illustrated the shift of the metal-semiconductor barrier due to Sb doping. This work provided an effective large-scale synthesis strategy for doping ZnO NWs in aqueous solution.
