| Autor: |
Silva, Reinaldo Correia, Terra, Fernanda Fernandes, Guise, Yuri Felipe, Prado, Marco Antônio Máximo, Prado, Vânia Ferreira, Hiyane, Meire Ioshie, Costa Malheiros, Denise Maria Avancini, Prado, Carla Maximo, Camara, Niels Olsen Saraiva, Braga, Tarcio Teodoro |
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| Zdroj: |
Pathophysiology; Sep2016, Vol. 23 Issue 3, p229-236, 8p |
| Abstrakt: |
Chronic kidney disease (CKD) is associated with several other long-lasting conditions such as diabetes and cardiovascular diseases and it is a significant contributor to mortality worldwide. Obstructive kidney disease is one of the leading causes of CKD in children and may result from a wide variety of pathologic processes. Recent studies have shown that α7 nicotinic acetylcholine receptor (α7 nAChR) activation in the cholinergic anti-inflammatory pathway reduces production of inflammatory mediators and consequently prevents tissue injury and death. Here, we examined the role of endogenous release of acetylcholine on the development of fibrosis in renal tissue using a model of unilateral ureter obstruction (UUO)-induced CKD, in which obstruction promotes inflammation-mediated kidney damages. To interfere with acetylcholine secretion, we used mice in which the vesicular acetylcholine transporter is genetically reduced (VAChT KD hom mice). We observed a higher renal damage in VAChT mutant mice when compared to wild type controls, exemplified by higher proteinuria and increased amount of type 1 collagen in the kidney tissue, indicating accentuated fibrogenesis. These results were accompanied by enhanced localized kidney inflammation, with increased T H 1/T H 17 profile response. Administration of PNU-282987, a selective agonist of α7 nAChR, significantly attenuated kidney injury after UUO in VAChT KD hom mice, indicating that the lack of acetylcholine release decrease the action of the cholinergic anti-inflammatory pathway, promoting an up-regulation of pro-inflammatory and pro-fibrotic pathways. These results suggest that physiological activation of the cholinergic anti-inflammatory pathway regulates inflammatory responses in the kidney suggesting a new therapeutic approach for kidney disease. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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