Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 133, Issue 4, Pages 203-213Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1016/j.jphs.2016.12.005
Keywords
beta-Aminoisobutyric acid; Angiotensin II; Extracellular matrix; Interleukin-17; Reactive oxygen species
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Renal fibrosis is a hallmark feature of chronic kidney disease, which is reflected by proliferation and migration of interstitial fibroblasts and extracellular matrix (ECM) accumulation. beta-Aminoisobutyric acid (BAIBA) is recently demonstrated to exert a protective role from metabolic diseases. However, whether and how BAIBA on fibroblast activation and renal fibrosis response to angiotensin II (Ang II) remains largely obscure. Herein, we showed that BAIBA significantly depressed the proliferation and migration of NRK-49F cells in vitro. Treatment with Ang II remarkably up-regulated the expressions of fibronectin (FN), collagen 1 (COL 1), alpha-smooth muscle actin (alpha-SMA), interleukin-17 (IL-17) and nicotinamide adenine dinucleotide phosphate oxidase (NOX2)-derived reactive oxygen species (ROS) production in cultured NRK-49F cells. Pretreatment with BAIBA almost blocked Ang II-induced ECM production and IL-17-mediated oxidative stress in NRK-49F cells. BAIBA treatment ameliorates fibroblasts activation and renal fibrosis in rat obstructed kidneys involving inhibition of Ang II/IL-17/ROS signaling transduction, which may be considered as a therapeutic candidate for fibrosis-related diseases. (C) 2017 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.
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