Abstract
Pulmonary emphysema is a disease in which alveoli in the lung are irreversibly destroyed, compromising lung function. All-trans-retinoic acid (ATRA) reportedly repairs the alveoli of emphysema model mice. In addition, ATRA can activate two nuclear receptors, nuclear retinoic acid receptor (RAR) and peroxisome proliferator-activated receptor (PPAR) β/δ. Both of these receptors induce differentiation in many different cell types. In this study, PPARβ/δ stimulation is shown to induce differentiation of human alveolar epithelial progenitor cells into alveolar type II epithelial (AT-II) cells. PPARβ/δ activation also stimulates the expression of adipose differentiation-related protein mRNA in human alveolar epithelial progenitor cells. These data suggest that PPARβ/δ selective agonists could differentiate human alveolar epithelial progenitor cells without cytotoxic of ATRA derived from stimulation to RAR.
Highlights
Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death according to a report released by World Health Organization in 2005, is an increasing global health problem
We have previously shown that All-trans-retinoic acid (ATRA) induces the differentiation of human Alveolar Epithelial Progenitor Cell (AEPC) to alveolar type II epithelial (AT-II) cells [3]; the mechanism by which ATRA induces AEPC differentiation remains unknown
We assessed the involvement of nuclear receptors retinoic acid receptor (RAR) and PPARβ/δ in the differentiation of human AEPCs using the RAR-selective ligand TTNPB and the PPARβ/δ-selective ligand GW0742
Summary
Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death according to a report released by World Health Organization in 2005, is an increasing global health problem. Human alveolar epithelial progenitor cells were incubated for indicated time or concentration of TTNPB or GW0742 in DMEM for and immunofluorescence staining cell count in 8well chamber (2 × 103/mL) and for western blot analysis in 6 well plate (5 × 103/mL), 0-48 hours in DMEM containing 1 μM GW0742 or ATRA for RT-PCR in 24 well plate (1 × 104/mL). ADRP: Adipose Differentiation-Related Protein; GAPDH: Glyceraldehyde3-Phosphate Dehydrogenase; PPAR: Peroxisome Proliferator-Activated Receptor was performed using Immobilon TM Western Chemiluminescent HRP Substrate (Millipore, USA) and following that user guide. Human alveolar epithelial progenitor cells were transfected with siRNA against PPARβ/δ and negative control (Ambion, Life Technologies,USA).
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