Rationale
Wnt/β-catenin signaling has an important role in the angiogenic activity of endothelial cells (ECs). Bach1 is a transcription factor and is expressed in ECs, but whether Bach1 regulates angiogenesis is unknown.
Objective
This study evaluated the role of Bach1 in angiogenesis and Wnt/β-catenin signaling.
Methods and Results
Hind-limb ischemia was surgically induced in Bach1−/− mice and their wild-type littermates and in C57BL/6J mice treated with adenoviruses coding for Bach1 or GFP. Lack of Bach1 expression was associated with significant increases in perfusion and vascular density and in the expression of proangiogenic cytokines in the ischemic hindlimb of mice, with enhancement of the angiogenic activity of ECs (eg, tube formation, migration, and proliferation). Bach1 overexpression impaired angiogenesis in mice with hind-limb ischemia and inhibited Wnt3a-stimulated angiogenic response and the expression of Wnt/β-catenin target genes, such as interleukin-8 and vascular endothelial growth factor, in human umbilical vein ECs. Interleukin-8 and vascular endothelial growth factor were responsible for the antiangiogenic response of Bach1. Immunoprecipitation and GST pull-down assessments indicated that Bach1 binds directly to TCF4 and reduces the interaction of β-catenin with TCF4. Bach1 overexpression reduces the interaction between p300/CBP and β-catenin, as well as β-catenin acetylation, and chromatin immunoprecipitation experiments confirmed that Bach1 occupies the TCF4-binding site of the interleukin-8 promoter and recruits histone deacetylase 1 to the interleukin-8 promoter in human umbilical vein ECs.
Conclusions
Bach1 suppresses angiogenesis after ischemic injury and impairs Wnt/β-catenin signaling by disrupting the interaction between β-catenin and TCF4 and by recruiting histone deacetylase 1 to the promoter of TCF4-targeted genes.
MR may interact with NFAT1 and activator protein-1 to control IFN-γ in T cells and to regulate target organ damage and ultimately BP. Targeting MR in T cells specifically may be an effective novel approach for hypertension treatment.
In this study, a fixed-site field experiment was conducted to study the influence of different combinations of tillage and straw incorporation management on carbon storage in different-sized soil aggregates and on crop yield after three years of rice-wheat rotation. Compared to conventional tillage, the percentages of >2 mm macroaggregates and water-stable macroaggregates in rice-wheat double-conservation tillage (zero-tillage and straw incorporation) were increased 17.22% and 36.38% in the 0–15 cm soil layer and 28.93% and 66.34% in the 15–30 cm soil layer, respectively. Zero tillage and straw incorporation also increased the mean weight diameter and stability of the soil aggregates. In surface soil (0–15 cm), the maximum proportion of total aggregated carbon was retained with 0.25–0.106 mm aggregates, and rice-wheat double-conservation tillage had the greatest ability to hold the organic carbon (33.64 g kg−1). However, different forms occurred at higher levels in the 15–30 cm soil layer under the conventional tillage. In terms of crop yield, the rice grown under conventional tillage and the wheat under zero tillage showed improved equivalent rice yields of 8.77% and 6.17% compared to rice-wheat double-cropping under zero tillage or conventional tillage, respectively.
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