Effect of recombinant human keratinocyte growth factor in inducing Ras–Raf–Erk pathway-mediated cell proliferation in emphysematous mice lung

Muyal, Jai Prakash; Kotnala, Sudhir; Bhardwaj, Harsh; Tyagi, Amit

doi:10.3109/08958378.2014.957426

Cited by 8 publications

(1 citation statement)

References 56 publications

(68 reference statements)

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“…Also, low concentrations of CS extract increased cell proliferation in vitro (57,58), consistent with our findings in vivo. However, PPE potently degrades lung extracellular matrix proteins that are crucial for the survival of lung structural cells, thus leading to reduced cell proliferation as reported previously (59,60). Therefore, it was not entirely surprising that PPE treatment in mice reduced cell proliferation.…”

Section: /2mentioning

confidence: 84%

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

Jiang¹,

Lao²,

Qiu³

et al. 2016

Am J Respir Crit Care Med

102

134

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Rationale: A genetic locus within the FAM13A gene has been consistently associated with chronic obstructive pulmonary disease (COPD) in genome-wide association studies. However, the mechanisms by which FAM13A contributes to COPD susceptibility are unknown.Objectives: To determine the biologic function of FAM13A in human COPD and murine COPD models and discover the molecular mechanism by which FAM13A influences COPD susceptibility. ) were generated and exposed to cigarette smoke. The lung inflammatory response and airspace size were assessed in Fam13a 2/2 and Fam13a 1/1 littermate control mice. Cellular localization of FAM13A protein and mRNA levels of FAM13A in COPD lungs were assessed using immunofluorescence, Western blotting, and reverse transcriptase-polymerase chain reaction, respectively. Immunoprecipitation followed by mass spectrometry identified cellular proteins that interact with FAM13A to reveal insights on FAM13A's function. ) were resistant to chronic cigarette smoke-induced emphysema compared with Fam13a 1/1 mice. In vitro, FAM13A interacts with protein phosphatase 2A and recruits protein phosphatase 2A with glycogen synthase kinase 3b and b-catenin, inducing b-catenin degradation. Fam13a 2/2 mice were also resistant to elastase-induced emphysema, and this resistance was reversed by coadministration of a b-catenin inhibitor, suggesting that FAM13A could increase the susceptibility of mice to emphysema development by inhibiting b-catenin signaling. Moreover, human COPD lungs had decreased protein levels of b-catenin and increased protein levels of FAM13A. Conclusions:We show that FAM13A may influence COPD susceptibility by promoting b-catenin degradation.

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