FIZZ1 potentiates the carbachol-induced tracheal smooth muscle contraction

Abstract

FIZZ1 is an adipokine highly expressed under inflammatory conditions, and yet, little is known of its function. In this study we examine the expression and function of FIZZ1 in an ovalbumin mouse model of asthma.Trachea from naïve or ovalbumin-sensitised and -challenged mice were compared for transcriptional, functional and proteomic differences using gene microarrays, ex vivo tracheal contraction, immunohistochemistry and Western blot analysis.FIZZ1 was expressed in ovalbumin-treated, but not naïve, trachea. Naïve trachea incubated with recombinant FIZZ1 exhibited denuded epithelium and contractile hyperresponsiveness. The FIZZ1-incubated trachea also exhibited an associated increased expression of phospho-c-Raf, phospho-extracellular signal-regulated kinase 1/2, phospho-p38, These data demonstrate that FIZZ1 regulates tracheal smooth muscle contraction through impairment of the epithelium and activation of the mitogen-activated protein kinase pathway in muscle.

RETRACTED: Macrophage phenotypic plasticity in atherosclerosis: The associated features and the peculiarities of the expression of inflammatory genes

“…Arg-1 utilizes arginine, a substrate for inducible NO synthase, and therefore diminishes NO production, a characteristic of the proinflammatory M1 macrophages [101]. FIZZ1 is induced by IL-4 and stimulates synthesis of collagen and α-smooth muscle actin in vascular smooth muscle cells (VSMCs) therefore contributing to plaque stabilization [102]. However, function of FIZZ1 in macrophages is unclear.…”

Resistin-Like Molecule alpha Enhances the Proliferation and Migration of Aortic Vascular Smooth Muscle Cells

“…It is also well documented that inflammatory Th2 cytokines stimulate macrophages to express RELMα, IL-4 and IL-13 [15]. Other studies have shown that the anoxic conditions that exist in the presence of atherosclerosis result in an upregulation of RELMα in the pulmonary vascular wall [11]. Expression of RELMα in activated macrophages and granulation tissue has also been demonstrated in the presence of parasitic infection and coexisting chronic inflammation [16,17].…”

“…RELMα is a members of the family of resistin-like molecules which is thought to play an important role in pulmonary fibrosis, asthma, hypoxia and silicosis [6,11,12,13]. Further studies have shown thatresistin-like molecules may be involved in the formation of foam cells and the development of angiogenesis and thrombosis, indicating that they support the progression of atherosclerosis [5,14].…”

Retnla Overexpression Attenuates Allergic Inflammation of the Airway

“…Recent studies showed that ERK activity was significantly higher in lungs of asthmatic mice than in those of normal controls [43], and that its inhibition had anti-inflammatory effects in OVA-induced mice, leading to reduced production of IL-4, IL-5, and IL-13, as well as decreased airway mucus production and airway hyperresponsiveness [31]. Previous studies have demonstrated that Retnla increased ERK activity, leading to smooth muscle contraction and prolonged survival of myofibroblasts [19], [44]. Those results suggest that Retnla may increase lung inflammation via ERK activation.…”

“…Counter to this, recent work using Retnla -deficient mice showed that Retnla is dispensable for Th2-associated allergen-driven lung inflammation [16], and another study reported that recombinant Retnla increased proliferation and growth factor expression in pulmonary endothelial cells [17], [18]. Moreover, recombinant Retnla increased carbachol-induced tracheal smooth muscle contraction through activation of mitogen-activated protein kinase (MAPK) signaling [19]. The direct administration of recombinant Retnla to mice promoted airway eosinophilia, fibrosis, and epithelial thickening [20].…”