A Chronic Obstructive Pulmonary Disease Susceptibility Gene, FAM13A, Regulates Protein Stability of β-Catenin

• DOI: 10.1164/rccm.201505-0999oc
• Publication Date: 2016-02-10T23:05:36Z
• Authors: Zhiqiang Jiang; Taotao Lao; Weiliang Qiu; Francesca Polverino; Kushagra Gupta; Feng Guo; John D. Mancini; Zun Zar Chi Naing; Michael H. Cho; Peter J. Castaldi; Yang Sun; Jane Yu; Maria E. Laucho-C...; Lester Kobzik; Benjamin A. Raby; Augustine M. K. Choi; Mark A. Perrella; Caroline A. Owen; Edwin K. Silverman; Xiaobo Zhou
• Keywords: Mice, Inbred C57BL; Mice, Knockout; Disease Models, Animal; Mice; Pulmonary Disease, Chronic Obstructive; Protein Stability; Animals; Humans; Female; Genetic Predisposition to Disease; beta Catenin; Signal Transduction; 3. Good health

A genetic locus within the FAM13A gene has been consistently associated with chronic obstructive pulmonary disease (COPD) in genome-wide association studies. However, mechanisms by which contributes to COPD susceptibility are unknown.To determine biologic function of human and murine models discover molecular mechanism influences susceptibility.Fam13a null mice (Fam13a(-/-)) were generated exposed cigarette smoke. The lung inflammatory response airspace size assessed Fam13a(-/-) Fam13a(+/+) littermate control mice. Cellular localization protein mRNA levels lungs using immunofluorescence, Western blotting, reverse transcriptase-polymerase chain reaction, respectively. Immunoprecipitation followed mass spectrometry identified cellular proteins that interact reveal insights on FAM13A's function.In lungs, is expressed airway alveolar type II epithelial cells macrophages. Fam13a resistant smoke-induced emphysema compared In vitro, interacts phosphatase 2A recruits glycogen synthase kinase 3β β-catenin, inducing β-catenin degradation. also elastase-induced emphysema, this resistance was reversed coadministration a inhibitor, suggesting could increase development inhibiting signaling. Moreover, had decreased increased FAM13A.We show may influence promoting