International journal of molecular medicine
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Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology with considerable morbidity and mortality. Seeking informative diagnostic markers with greater clinical significance is essential for the early diagnosis of IPF. microRNAs (miRNAs or miRs) have emerged as novel serum diagnostic biomarkers for various diseases. In this study, we performed microarray analysis of the miRNA expression profile in the serum of patients with IPF compared to that of control subjects. ⋯ The results from this study provide evidence to link the biological role of miRNAs to IPF, and suggest that miRNAs may undertake a variety of functions. Additionally, we found that the altered expression levels of miR-21, miR-155 and miR-101-3p were associated with forced vital capacity (FVC) and radiological features in IPF. Our data may serve as a basis for further investigation, preferably in large prospective studies, before miRNA can be used as a non-invasive screening tool for IPF in routine clinical practice.
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Mitochondrial DNA (mtDNA) contains unmethylated CpG motifs that exhibit immune stimulatory capacities. The aim of this study was to investigate whether mtDNA activates the Toll-like receptor 9 (TLR9)/nuclear factor-κB (NF-κB) pathway, thereby contributing to post-traumatic systemic inflammatory response syndrome (SIRS) and lung injury in rats. The effects of mtDNA on macrophage culture were examined in order to elucidate the putative cellular mechanisms. ⋯ In addition, mtDNA increased serum tumor necrosis factor-α, interleukin (IL)-6 and IL-10 levels in vivo and increased their secretion by cultured macrophages (p<0.05). In lung tissue, mtDNA increased NF-κB, IκB-α and TLR9 mRNA levels (p<0.05); it also increased phosphorylated NF-κB p65 and TLR9 protein levels in the macrophage cultures. Thus, mtDNA may be part of the danger-associated molecular patterns, contributing to the initiation of sterile SIRS through the activation of the TLR9/NF-κB pathway and the induction of pro-inflammatory cytokine production.
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Podocytes are terminally differentiated epithelial cells lacking the ability to proliferate. The loss of podocytes is a hallmark of progressive kidney diseases, including diabetic nephropathy (DN). Endoplasmic reticulum stress (ERS)-induced apoptosis is involved in a number of pathological conditions, including DN. ⋯ CHOP/GADD153 expression reached its peak at 48 h, and caspase-12 expression gradually increased with time. Spearman's correlation analysis revealed that caspase-12 and CHOP/GADD153 positively correlated with the apoptotic rate (r=0.915, P<0.01 and r=0.639, P<0.01). Our results demonstrated that hyperglycemia (high glucose) induced apoptosis partly through ERS in the differentiated mouse podocytes, which possibly contributes to the pathogenesis of DN.
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Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease with unknown etiology and undefined treatment modality. Fibroblasts are regarded as the major cell type that mediates the onset and progression of lung fibrosis by secreting large amounts of extracellular matrix (ECM) proteins, such as connective tissue growth factor (CTGF/CCN2). Current knowledge confers a crucial role of CCN2 in lung fibrosis. ⋯ The TGF-β1-induced upregulation of the phosphorylation of Akt was reversed by CCN5 overexpression. Our results also demonstrated that adenovirus-mediated CCN5 overexpression in a mouse model of bleomycin-induced IPF significantly decreased the hydroxyproline content in the lungs, as well as TGF-β1 expression in bronchoalveolar lavage fluid. Taken together, our data demonstrate that CCN5 exerts an inhibitory effect on the fibrotic phenotypes of pulmonary fibroblasts in vitro and in vivo, and as such may be a promising target for the treatment of IPF.
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The creation of functional muscles/muscle tissue from human stem cells is a major goal of skeletal muscle tissue engineering. Mesenchymal stem cells (MSCs) from fat/adipose tissue (AT-MSCs), as well as bone marrow (BM-MSCs) have been shown to bear myogenic potential, which makes them candidate stem cells for skeletal muscle tissue engineering applications. The aim of this study was to analyse the myogenic differentiation potential of human AT-MSCs and BM-MSCs cultured in six different cell culture media containing different mixtures of growth factors. ⋯ The strongest DES expression was observed using the 30% conditioned cell culture medium. The detection of myogenic markers using different cell culture media as stimuli was only achieved in the AT-MSCs, but not in the BM-MSCs. The strongest myogenic differentiation, in terms of the markers examined, was induced by the 30% conditioned cell culture medium.