Conditioned Media of Adipose-Derived Stem Cells Suppresses Sidestream Cigarette Smoke Extract Induced Cell Death and Epithelial-Mesenchymal Transition in Lung Epithelial Cells
Abstract
:1. Introduction
2. Results
2.1. CSE Induces Lung Epithelial Cell Death in Concentration- and Serum-Dependent Manners
2.2. ADSC-Conditioned Medium Protected Cells from CSE-Induced Epithelial Cell Death
2.3. ADSC-CM Reduces CSE-Induced EMT in A549 Cells
2.4. Gene Expression Profiles of A549 Cells Responding to CSE or TGF-β1
2.5. ADSC-CM Inhibits Both CSE and TGF-β1 Induced Epithelial Cell Migration
3. Discussion
4. Materials and Methods
4.1. Chemicals and Culture Medium
4.2. Preparation of ADSC-Conditioned Medium
4.3. Cell Injury Induced by Cigarette Smoke Extract Exposure
4.4. Gene Expression Analysis
4.5. Immunoblotting and Fluorescence Detection
4.6. Cell Migration Assay
4.7. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
TGF | Transforming Growth Factor |
TNF | Tumor Necrosis Factor |
ADSC-CM | Adipose Derived Stem Cell-Conditioned Medium |
CSE | Cigarette Smoke Extract |
COPD | Chronic Obstructive Pulmonary Disease |
URA | Upstream Regulator Analysis |
EMT | Epithelial-to-Mesenchymal Transition |
LDH | Lactate Dehydrogenase |
MSC | Mesenchymal Stem Cell |
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Upstream Regulator | Molecule Type | Predicted State | z-Score | p-Value of Overlap |
---|---|---|---|---|
NUPR1 | transcription regulator | Activated | 9.495 | 5.38 × 10−50 |
TP53 | transcription regulator | Activated | 6.814 | 3.51 × 10−46 |
E2F4 | transcription regulator | 1.65 × 10−38 | ||
ERBB2 | kinase | Activated | 2.186 | 3.28 × 10−35 |
TGFB1 | growth factor | Activated | 3.746 | 3.18 × 10−32 |
FOXO1 | transcription regulator | −1.594 | 4.04 × 10−23 | |
FOXM1 | transcription regulator | Inhibited | −4.121 | 5.29 × 10−21 |
E2f | group | Inhibited | −3.317 | 2.44 × 10−20 |
CCND1 | transcription regulator | −0.468 | 7.58 × 10−20 | |
E2F1 | transcription regulator | 2.30 × 10−19 | ||
CDKN1A | kinase | Activated | 4.263 | 5.50 × 10−17 |
CDK4 | kinase | 1.78 × 10−16 | ||
ESR1 | ligand-dependent nuclear receptor | −0.519 | 4.03 × 10−15 | |
TP63 | transcription regulator | −0.619 | 7.11 × 10−15 | |
KDM5B | transcription regulator | Activated | 4.874 | 1.41 × 10−14 |
S100A6 | transporter | Inhibited | −3.742 | 1.60 × 10−14 |
TREM1 | transmembrane receptor | 0.769 | 2.85 × 10−14 | |
TNF | cytokine | Activated | 3.127 | 1.80 × 10−12 |
E2F6 | transcription regulator | Activated | 3.162 | 7.50 × 10−12 |
P38 MAPK | group | 1.399 | 9.32 × 10−12 | |
AR | ligand-dependent nuclear receptor | −1.381 | 1.51 × 10−11 | |
BRCA1 | transcription regulator | 1.564 | 5.50 × 10−11 | |
HDAC1 | transcription regulator | 1.35 × 10−10 | ||
ATF3 | transcription regulator | 1.134 | 1.52 × 10−10 | |
estrogen receptor | group | Inhibited | −3.329 | 8.48 × 10−10 |
Upstream Regulator | Molecule Type | Predicted State | z-Score | p-Value of Overlap |
---|---|---|---|---|
TGFB1 | growth factor | Activated | 6.637 | 1.43 × 10−36 |
TNF | cytokine | 1.508 | 6.20 × 10−33 | |
estrogen receptor | group | Inhibited | −3.797 | 3.75 × 10−29 |
ERBB2 | kinase | Activated | 4.162 | 1.27 × 10−25 |
JUN | transcription regulator | 0.595 | 7.24 × 10−25 | |
WISP2 | growth factor | Inhibited | −2.947 | 7.22 × 10−18 |
TREM1 | transmembrane receptor | −0.563 | 1.10 × 10−17 | |
IL1A | cytokine | Activated | 2.028 | 4.32 × 10−16 |
HNRNPA2B1 | other | 6.99 × 10−16 | ||
ERK | group | 1.713 | 2.47 × 10−15 | |
HDAC6 | transcription regulator | Activated | 3.375 | 3.41 × 10−15 |
Cg | complex | Activated | 2.661 | 2.01 × 10−14 |
SPDEF | transcription regulator | Inhibited | −3.174 | 5.92 × 10−14 |
CTNNB1 | transcription regulator | 1.071 | 6.00 × 10−14 | |
P38 MAPK | group | 1.489 | 1.06 × 10−13 | |
COL18A1 | other | Inhibited | −3.022 | 1.08 × 10−13 |
SP1 | transcription regulator | 0.862 | 1.57 × 10−13 | |
ITGB1 | transmembrane receptor | 0.639 | 4.14 × 10−13 | |
NEUROG1 | transcription regulator | −1.342 | 1.42 × 10−12 | |
AR | ligand-dependent nuclear receptor | −0.101 | 2.34 × 10−12 | |
TP63 | transcription regulator | 0.650 | 7.08 × 10−12 | |
IL1B | cytokine | 0.154 | 9.64 × 10−12 | |
KIAA1524 | other | Inhibited | −2.233 | 1.04 × 10−11 |
TGM2 | enzyme | −0.168 | 1.47 × 10−11 | |
HIF1A | transcription regulator | 1.337 | 2.12 × 10−11 |
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Chen, T.-Y.; Liu, C.-H.; Chen, T.-H.; Chen, M.-R.; Liu, S.-W.; Lin, P.; Lin, K.M.-C. Conditioned Media of Adipose-Derived Stem Cells Suppresses Sidestream Cigarette Smoke Extract Induced Cell Death and Epithelial-Mesenchymal Transition in Lung Epithelial Cells. Int. J. Mol. Sci. 2021, 22, 12069. https://doi.org/10.3390/ijms222112069
Chen T-Y, Liu C-H, Chen T-H, Chen M-R, Liu S-W, Lin P, Lin KM-C. Conditioned Media of Adipose-Derived Stem Cells Suppresses Sidestream Cigarette Smoke Extract Induced Cell Death and Epithelial-Mesenchymal Transition in Lung Epithelial Cells. International Journal of Molecular Sciences. 2021; 22(21):12069. https://doi.org/10.3390/ijms222112069
Chicago/Turabian StyleChen, Tzu-Yin, Chia-Hao Liu, Tsung-Hsien Chen, Mei-Ru Chen, Shan-Wen Liu, Pinpin Lin, and Kurt Ming-Chao Lin. 2021. "Conditioned Media of Adipose-Derived Stem Cells Suppresses Sidestream Cigarette Smoke Extract Induced Cell Death and Epithelial-Mesenchymal Transition in Lung Epithelial Cells" International Journal of Molecular Sciences 22, no. 21: 12069. https://doi.org/10.3390/ijms222112069