Background: Oxidative stress has been identified as an important pathogenesis mechanism in the development of renal interstitial fibrosis in unilateral ureteral obstruction (UUO). Previous studies have demonstrated increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOXs) in response to UUO. We aimed to investigate whether NOXs activation was involved in the development of renal fibrosis in UUO by contribution to oxidative stress and the potential mechanism in the present study.
Methods: Apocynin, a NOXs inhibitor, was initiated immediately by gavage after UUO was performed on Wistar rats and continued until 7 days after UUO. Changes of markers of oxidative stress, renal macrophage infiltration and fibrosis, TGF-β1 expression, NOXs expression and activity, and ERK activation were evaluated.
Results: Apocynin significantly attenuated the activity of NOXs, accompanied with decreased expression of NOX2, NOX4, and oxidative stress markers in the obstructed kidneys of UUO. Additionally, collagen deposition and renal fibrosis induced by UUO were attenuated by apocynin treatment. Furthermore, apocynin treatment significantly attenuated the phosphorylation of ERK, accumulation of myofibroblast and infiltration of macrophage in obstructed kidneys. No significant effect of apocynin on UUO-induced increased TGF-β1 expression could be observed. And there was no significant change of anti-oxidants enzyme activities in the obstructed kidneys of apocynin-treated rats.
Conclusions: These results suggested that apocynin might exert beneficial effects on renal fibrosis by inhibition of NOXs activation and subsequent reduction of oxidative stress, ERK activation, and myofibroblast accumulation in UUO rats. Targeting NOXs may serve as a therapeutic strategy for the treatment of renal fibrosis. 相似文献
Abstract: A silicified brachiopod fauna from the Middle Ordovician Kuniutan Formation (lower–middle Darriwilian, i.e. uppermost Arenig to lower Llanvirn) at Wudang, Guiyang, central Guizhou, South China, includes abundant specimens of Yangtzeella, Orthambonites and Leptellina together with common Parisorthis, Saucrorthis, rare Anomalorthis?, Hemipronites?, Leptestia? and, significantly, Aporthophyla; associated are rare trilobites, gastropods, crinoids and nautiloids. The Yangtzeella kueiyangensis‐Orthambonites delicata Association is defined for this shallow‐water, Benthic Assemblage 3, association. This first record of Aporthophyla in South China may indicate a link between South China and the Toquima‐Table Head Province, where the Aporthophyla fauna is more typically developed. However, this association is significantly different from the latter in having three endemic genera, Yangtzeella, Saucrorthis and Parisorthis, rare numbers of Aporthophyla and Anomalorthis?, and the absence of many other typical elements of the Aporthophyla fauna. The occurrence of Orthambonites, Hemipronites? and Leptestia? suggests some relationships between South China and the Baltic Platform during the Mid Ordovician. The various brachiopod associations bearing Aporthophyla may be quite different in nature, composition and diversity, and may possess different background palaeobiogeographical signatures. The assemblages containing Aporthophyla in South China, Qaidam, Malaysia, Australia and possibly Tibet are clearly different biogeographically from those associated with the Toquima‐Table Head and the Celtic provinces. Two new species, Aporthophyla sinensis sp. nov. and Leptellina orientalis sp. nov. are described. 相似文献
Receptor activator of NF‐κB ligand (RANKL) is essential for osteoclast formation and bone remodeling. Nevertheless, the cellular source of RANKL for osteoclastogenesis has not been fully uncovered. Different from peripheral adipose tissue, bone marrow (BM) adipose lineage cells originate from bone marrow mesenchymal stromal cells (BMSCs). Here, we demonstrate that adiponectin promoter‐driven Cre expression (AdipoqCre) can target bone marrow adipose lineage cells. We cross the AdipoqCre mice with ranklfl/fl mice to conditionally delete RANKL from BM adipose lineage cells. Conditional deletion of RANKL increases cancellous bone mass of long bones in mice by reducing the formation of trabecular osteoclasts and inhibiting bone resorption but does not affect cortical bone thickness or resorption of calcified cartilage. AdipoqCre; ranklfl/fl mice exhibit resistance to estrogen deficiency and rosiglitazone (ROS)‐induced trabecular bone loss but show bone loss induced by unloading. BM adipose lineage cells therefore represent an essential source of RANKL for the formation of trabecula osteoclasts and resorption of cancellous bone during remodeling under physiological and pathological conditions. Targeting bone marrow adiposity is a promising way of preventing pathological bone loss. 相似文献