Wnt-4 and Ets-1 signaling pathways for regeneration after acute renal failure

Ischemic acute renal failure (ARF) is the most common form of ARF in the adult population. The molecular mechanisms of tubular regeneration after ischemic renal injury remain largely unknown. An understanding of the mechanisms that lead to renal cell proliferation and regeneration will be necessary for the exploration of novel therapeutic strategies for the treatment of ARF. It has been suggested that regeneration processes may recapitulate developmental processes in order to restore organ or tissue function. The adult tubular epithelial cells have a potent ability of regenerate after cellular damage. We examined functional role of two developmental genes, Wnt-4 and Ets-1, in renal tubular regeneration in ARF. The Wnt-β-catenin pathway plays key roles in embryogenesis. Wnt-4 is known to be expressed in the mesonephric duct in the embryonic development. To clarify the significance of the Wnt-4-β-catenin pathway in ARF, we used a rat ARF model in vivo and LLC-PK1 cells as an in vitro model. After clamping left rat renal artery for 1 hour, we examined whole kidney homogenate and total RNA extracted at 3, 6, 12, 24, 48, and 72 hours after reperfusion by Western blot analysis and real-time reverse transcription-polymerase chain reaction (RT-PCR). Wnt-4 mRNA and protein expression were strongly increased at 3 to 12 hours and 6 to 24 hours after ischemia, respectively. In immunohistologic examination, Wnt-4 was expressed in the proximal tubules and coexpressed with aquaporin 1 and proliferating cell nuclear antigen (PCNA). Cyclin D1 and cyclin A were expressed at 12 to 48 hours after reperfusion. Furthermore, overexpression of Wnt-4 and β-catenin promoted the cell cycle and increased the promoter activity and protein expression of cyclin D1 and cyclin A in LLC-PK1 cells. These data suggest that the Wnt-4-β-catenin pathway plays a key role in the cell cycle progression of renal tubules in ARF. The Ets family of transcription factors is defined by a conserved DNA-binding Ets domain that forms a winged helix-turn-helix structure motif. The Ets family is involved in a diverse array of biologic functions, including cellular growth, migration, and differentiation. To clarify the significance of Ets-1 in ARF, we used a rat ARF model in vivo and LLC-PK1 cells as an in vitro model. Ets-1 mRNA and protein expression were strongly increased at 3 to 12 hours and 6 to 24 hours after the ischemia, respectively. In the immunohistologic examination, Ets-1 was expressed in the proximal tubules and coexpressed with PCNA. Furthermore, overexpression of Ets-1 promoted the cell cycle and increased the promoter activity and protein expression of cyclin D1 in LLC-PK1 cells. Ets-1 promoter activity increased between 3 hours and 6 hours in hypoxia, and hypoxia also induced changes in the Ets-1 protein level in LLC-PK1 cells. Taken together, these data suggest that Ets-1 plays a key role in the cell cycle progression of renal tubules in ARF. Our data suggest that Wnt-4-β-catenin and Ets-1 pathways regulate the transcription of cyclin D1 and control the regeneration of renal tubules in ARF. These developmental genes may play key roles in dedifferentiation and regeneration of the renal tubular cells after ARF

Laboratory testing of airborne brake wear particle emissions using a dynamometer system under urban city driving cycles

AbstractTo measure driving-distance-based mass emission factors for airborne brake wear particulate matter (PM; i.e., brake wear particles) related to the non-asbestos organic friction of brake assembly materials (pads and lining), and to characterize the components of brake wear particles, a brake wear dynamometer with a constant-volume sampling system was developed. Only a limited number of studies have investigated brake emissions under urban city driving cycles that correspond to the tailpipe emission test (i.e., JC08 or JE05 mode of Japanese tailpipe emission test cycles). The tests were performed using two passenger cars and one middle-class truck. The observed airborne brake wear particle emissions ranged from 0.04 to 1.4 mg/km/vehicle for PM10 (particles up to 10 μm (in size), and from 0.04 to 1.2 mg/km/vehicle for PM2.5. The proportion of brake wear debris emitted as airborne brake wear particles was 2–21% of the mass of wear. Oxygenated carbonaceous components were included in the airborne PM but not in the original friction material, which indicates that changes in carbon composition occurred during the abrasion process. Furthermore, this study identified the key tracers of brake wear particles (e.g., Fe, Cu, Ba, and Sb) at emission levels comparable to traffic-related atmospheric environments

The combined effect in one space dimension beyond the general theory for nonlinear wave equations

In this paper, we show the so-called "combined effect" of two different kinds of nonlinear terms for semilinear wave equations in one space dimension. Such a special phenomenon appears only in the case that the total integral of the initial speed is zero. It is remarkable that, including the combined effect case, our results on the lifespan estimates are partially better than those of the general theory for nonlinear wave equations.Comment: 42 pages. In the second version, the main modification in the second version is the improvement on the regularity of the solution for 1<p,q<2, which was caused by trivial oversight. We have the solution in the classical sense all the time. This version is accepted for the publication in the journal, Communications on Pure and Applied Analysis on 15/02/202