Nicotine: The link between cigarette smoking and the progression of renal injury?

Edgar A. Jaimes, Run Xia Tian, Leopoldo Raij

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

Cigarette smoke (CS) is the most important source of preventable morbidity and mortality in the United States. Recent clinical studies have suggested that, in addition to being a major cardiovascular risk factor, CS promotes the progression of kidney disease. The mechanisms by which CS promotes the progression of chronic kidney disease have not been elucidated. Here we demonstrate for the first time that human mesangial cells (MCs) are endowed with the nicotinic ACh receptors (nAChRs) α4, α5, α7, β2, β3, and β4. Studies performed in other cell types have shown that these nAChRs are ionotropic receptors that function as agonist-regulated Ca 2+ channels. Nicotine induced MC proliferation in a dose-dependent manner. At 10-7 M, a concentration found in the plasma of active smokers, nicotine induced MC proliferation [control, 1,328 ± 50 vs. nicotine, 2,761 ± 90 counts/minute (cpm); P < 0.05] and increased the synthesis of fibronectin (50%), a critical matrix component involved in the progression of chronic kidney disease. We and others have shown that, in response to PKC activation, MC synthesize reactive oxygen species (ROS) via NADPH oxidase. In the current studies we demonstrate that PKC inhibition as well as diphenyleneiodonium and apocynin, two inhibitors of NADPH oxidase, prevented the effects of nicotine on MC proliferation and fibronectin production, hence establishing ROS as second messengers of the actions of nicotine. Furthermore, nicotine increased the production of ROS as assessed by 2′,7′- dichlorofluorescein diacetate fluorescence [control, 184.4 ± 26 vs. nicotine, 281.5 ± 26 arbitrary fluorescence units (AFU); n = 5 experiments, P < 0.05]. These studies unveil previously unrecognized mechanisms that indict nicotine, a component of CS, as an agent that may accelerate and promote the progression of kidney disease.

Original languageEnglish (US)
Pages (from-to)H76-H82
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number1
DOIs
StatePublished - Jan 1 2007

Keywords

  • Cell proliferation
  • Extracellular matrix
  • Glomerular mesangium
  • Reactive oxygen species

ASJC Scopus subject areas

  • Physiology

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