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2015 ; 16
(ä): 124
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Down-regulation of USP13 mediates phenotype transformation of fibroblasts in
idiopathic pulmonary fibrosis
#MMPMID26453058
Geng J
; Huang X
; Li Y
; Xu X
; Li S
; Jiang D
; Liang J
; Jiang D
; Wang C
; Dai H
Respir Res
2015[Oct]; 16
(ä): 124
PMID26453058
show ga
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized
by fibroblastic foci and progressive scarring of the pulmonary parenchyma. IPF
fibroblasts display increased proliferation and enhanced migration and invasion,
analogous to cancer cells. This transformation-like phenotype of fibroblasts
plays an important role in the development of pulmonary fibrosis, but the
mechanism for this is not well understood. METHODS: In this study, we compared
gene expression profiles in fibrotic lung tissues from IPF patients and normal
lung tissues from patients with primary spontaneous pneumothorax using a cDNA
microarray to examine the mechanisms involved in the pathogenesis of IPF. In a
cDNA microarray, we found that USP13 was decreased in lung tissues from patients
with IPF, which was further confirmed by results from immunohistochemistry and
western blot assays. Then, we used RNA interference in MRC-5 cells to inhibit
USP13 and evaluated its effects by western blot, real-time RT-PCR,
bromodeoxyuridine incorporation, and transwell assays. We also used
co-immunoprecipitation and immunofluorescence staining to identify the
correlation between USP13 and PTEN in IPF. RESULTS: USP13 expression levels were
markedly reduced in fibroblastic foci and primary IPF fibroblast lines. The
depletion of USP13 resulted in the transformation of fibroblasts into an
aggressive phenotype with enhanced proliferative, migratory, and invasive
capacities. Additionally, USP13 interacted with PTEN and mediated PTEN
ubiquitination and degradation in lung fibroblasts. CONCLUSIONS: Down-regulation
of USP13 mediates PTEN protein loss and fibroblast phenotypic change, and thereby
plays a crucial role in IPF pathogenesis.