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2015 ; 2
(ä): 68
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Inflammatory Gene Expression Upon TGF-?1-Induced p38 Activation in Primary
Dupuytren s Disease Fibroblasts
#MMPMID26697433
Bujak M
; Ratkaj I
; Markova-Car E
; Juri?i? D
; Horvati? A
; Vu?ini? S
; Lerga J
; Baus-Lon?ar M
; Paveli? K
; Kraljevi? Paveli? S
Front Mol Biosci
2015[]; 2
(ä): 68
PMID26697433
show ga
OBJECTIVES: Inflammation is an underlying mechanism behind fibrotic processes and
differentiation of cells into myofibroblasts. Presented study therefore provides
new data on activation of autoimmune and inflammatory immune response genes that
accompany activation of p38 and cell differentiation in primary cells derived
from Dupuytren's disease (DD) patients. METHODS: Primary non-Dupuytren's disease
cells (ND) were isolated from macroscopically unaffected palmar fascia adjacent
to diseased tissue obtained from patients diagnosed with the last stage of DD and
cultured in vitro. Gene expression, collagen gel contraction assay and analysis
of secreted proteins were performed in ND cells treated with TGF-?1 and/or
inhibitor of p38 phosphorylation. RESULTS: During differentiation of ND
fibroblasts, increased expression of immune response genes PAI-1, TIMP-1, CCL11,
and IL-6 was found. These changes were accompanied by increased cell
contractility and activation of p38 and its target kinase MK2. Inhibition of p38
phosphorylation reversed these processes in vitro. CONCLUSIONS: TGF-?1 induced
p38 phosphorylation in ND cells grown from macroscopically unaffected palmar
fascia adjacent to diseased tissue from DD patients. This was accompanied by
activation of the cytokine genes CCL-11 and IL-6 and secretion of extracellular
matrix regulatory proteins PAI-1 and TIMP-1. A combined approach directed toward
inflammation and p38 MAPK-mediated processes in DD might be considered for
improving management of DD patients and prevention of recurrence.