TGF-β Mediated Epithelial-Mesenchymal Transition in Autosomal Dominant Polycystic Kidney Disease

Purpose: Recent studies have showed that epithelial-mesen-chymal transition (EMT) is a key process of glomerular and tubulointerstitial pathology in many chronic kidney diseases. However, there are no data of EMT in humane autosomal dominant polycystic kidney disease (ADPKD). Patients and Methods: ADPKD kidneys (N = 5) with end stage renal disease (ESRD) and control kidneys (N = 4) were analyzed immnunohistochemically. We evaluated α-SMA, E-cadherin, vimentin, TGF-β1 and Smad 2/3 expression in ADPKD and compared them with those in control kidney. These immuno-histochemical findings were quantitatively analyzed by com-puter-assisted image analyzer and positive tubules (%). Results: There were severe interstitial fibrosis and prolifera-tion of α-SMA+ myofibroblasts in ADPKD. Cystic tubular epithelial cells in ADPKD lost epithelial marker (E-cadherin) and expressed mesenchymal markers (α-SMA, vimentin). There were significant increases of α-SMA (34.3 ± 11.7 % vs 0.9 ± 1.5%), vimentin (19.9 ± 3.9 % vs 3.3 ± 1.4%), TGF-β1 (5.42 ± 2.83 % vs 0%) and Smad 2/3 (3.4 ± 1.7 % vs 0.7 ± 0.6%) in ADPKD kidneys compared with control kidneys evidenced by computer-assisted image analyzer. When we analyze the posi-tive tubules (%), the results were the same as computer-assisted image analyzer. Conclusion: Our results showed that the end stage of ADPKD is associated with TGF-β, Smad 2/3 and markers of EMT. It suggests that TGF-β mediated EMT has a role in progression of ADPKD. Key Words: Epithelial mesenchymal transition, antosomal dominant polycystic kidney diseas

Effects of Corni fructus on ovalbumin-induced airway inflammation and airway hyper-responsiveness in a mouse model of allergic asthma

<p>Abstract</p> <p>Background</p> <p>Allergic asthma is a chronic inflammatory lung disease that is characterized by airway hyperresponsiveness (AHR) to allergens, airway oedema, increased mucus secretion, excess production of T helper-2 (Th2) cytokines, and eosinophil accumulation in the lungs. Corni fructus (CF) is a fruit of <it>Cornus officinalis </it>Sieb. Et. Zucc. (Cornaceae) and has been used in traditional Korean medicine as an anti-inflammatory, analgesic, and diuretic agent. To investigate the anti-asthmatic effects of CF and their underlying mechanism, we examined the influence of CF on the development of pulmonary eosinophilic inflammation and airway hyperresponsiveness in a mouse model of allergic asthma.</p> <p>Methods</p> <p>In this study, BALB/c mice were systemically sensitized to ovalbumin (OVA) by intraperitoneal (i.p.), intratracheal (i.t.) injections and intranasal (i.n.) inhalation of OVA. We investigated the effect of CF on airway hyperresponsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production, and OVA-specific immunoglobulin E (IgE) production.</p> <p>Results</p> <p>The CF-treated groups showed suppressed eosinophil infiltration, allergic airway inflammation, and AHR via reduced production of interleuin (IL) -5, IL-13, and OVA-specific IgE.</p> <p>Conclusions</p> <p>Our data suggest that the therapeutic effects of CF in asthma are mediated by reduced production of Th2 cytokines (IL-5), eotaxin, and OVA-specific IgE and reduced eosinophil infiltration.</p

Quantization of virtual Grothendieck rings and their structure including quantum cluster algebras

The quantum Grothendieck ring of a certain category of finite-dimensional modules over a quantum loop algebra associated with a complex finite-dimensional simple Lie algebra $\mathfrak{g}$ has a quantum cluster algebra structure of skew-symmetric type. Partly motivated by a search of a ring corresponding to a quantum cluster algebra of {\em skew-symmetrizable} type, the quantum {\em virtual} Grothendieck ring, denoted by $\mathfrak{K}_q(\mathfrak{g})$, is recently introduced by Kashiwara--Oh \cite{KO23} as a subring of the quantum torus based on the $(q,t)$-Cartan matrix specialized at $q=1$. In this paper, we prove that $\mathfrak{K}_q(\mathfrak{g})$ indeed has a quantum cluster algebra structure of skew-symmetrizable type. This task essentially involves constructing distinguished bases of $\mathfrak{K}_q(\mathfrak{g})$ that will be used to make cluster variables and generalizing the quantum $T$-system associated with Kirillov--Reshetikhin modules to establish a quantum exchange relation of cluster variables. Furthermore, these distinguished bases naturally fit into the paradigm of Kazhdan--Lusztig theory and our study of these bases leads to some conjectures on quantum positivity and $q$-commutativity

Antiasthmatic Effects of Hesperidin, a Potential Th2 Cytokine Antagonist, in a Mouse Model of Allergic Asthma

Background and Objective. The features of asthma are airway inflammation, reversible airflow obstruction, and an increased sensitivity to bronchoconstricting agents, termed airway hyperresponsiveness (AHR), excess production of Th2 cytokines, and eosinophil accumulation in the lungs. To investigate the antiasthmatic potential of hesperidin as well as the underlying mechanism involved, we studied the inhibitory effect and anti-inflammatory effect of hesperidin (HPN) on the production of Th2 cytokines, eotaxin, IL-17, -OVA-specific IgE in vivo asthma model mice. Methods. In this paper, BALB/c mice were systemically sensitized to ovalbumin (OVA) followed intratracheally, intraperitoneally, and by aerosol allergen challenges. We investigated the effect of HPN on airway hyperresponsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production and OVA-specific IgE production in a mouse model of asthma. Results. In BALB/c mice, we found that HPN-treated groups had suppressed eosinophil infiltration, allergic airway inflammation, and AHR, and these occurred by suppressing the production of IL-5, IL-17, and OVA-specific IgE. Conclusions. Our data suggest that the therapeutic mechanism by which HPN effectively treats asthma is based on reductions of Th2 cytokines (IL-5), eotaxin, OVA-specific IgE production, and eosinophil infiltration via inhibition of GATA-3 transcription factor