Systems Biology Analysis of Temporal Dynamics That Govern Endothelial Response to Cyclic Stretch
Abstract
:1. Introduction
2. Materials and Methods
2.1. Endothelial Cell Culture
2.2. Cyclic Stretch
2.3. RNA Sequencing
2.4. Pathway Analysis
2.5. Immunofluorescence and Western Blotting
2.6. Quantitative PCR
2.7. Atomic Force Microscopy
3. Results
3.1. Cyclic Stretch Validation
3.2. Cell Cycle Regulation
3.3. Inflammatory Response
3.4. Fatty Acid Metabolism
3.5. mTOR Signaling
3.6. Regulation of Cell Stiffness by Cyclic Stretch
3.7. Cytoskeletal Remodeling
3.8. Shear Stress Comparison
3.9. qPCR Expression Validation
4. Discussion
4.1. Endothelial Response to Cyclic Stretch
4.2. Effect of Cyclic Stretch on the Endothelial Cytoskeleton
4.3. Comparison of Endothelial Response to Cyclic Stretch and Shear Stress
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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CDK2 (49) | PCNA (40) | RPA1 (39) | CDK1 (35) | BRCA1 (32) | MCM2 (32) |
---|---|---|---|---|---|
PA2G4 | USP1 | TIPIN | TIPIN | ORC2 | RPA3 |
PAICS | TIMELESS | EXOSC8 | EXOSC8 | MSH6 | ORC2 |
MYBL2 | POLD3 | SMC4 | SMC4 | CCNB1 | PLK1 |
HMGA1 | POLD2 | TMPO | TMPO | H2AFX | CDK6 |
CCNE2 | POLD1 | CHTF18 | CHTF18 | HMMR | ORC5 |
HMGB2 | RPA1 | UNG | UNG | CDK4 | L3MBTL1 |
CDKN3 | RPA2 | NOP56 | NOP56 | TUBB | MCM7 |
CKS2 | RPA3 | RFC2 | RFC2 | EZH2 | ORC4 |
CCNA1 | RFC2 | RFC3 | RFC3 | MYC | MCM5 |
CDC25A | RFC3 | SNRPB | SNRPB | UBE2T | GINS3 |
GMNN | CHTF18 | RPA3 | RPA3 | MLH1 | CDC6 |
CKS1B | HUS1 | PAN2 | PAN2 | DBF4 | CDK4 |
CDC20 | MLH1 | RPA2 | RPA2 | MSH3 | ORC6 |
CDC7 | DSCC1 | POLD1 | POLD1 | CHEK2 | MCM3 |
DBF4 | POLE | PCNA | PCNA | RBBP7 | DBF4 |
MCM4 | UNG | TOP2A | TOP2A | DDX39A | CCNB2 |
MCM6 | PMS2 | MSH3 | MSH3 | ORC3 | CDC45 |
CDC45 | TOP2A | HUS1 | HUS1 | BARD1 | MCM4 |
ORC2 | MSH3 | RAD9A | RAD9A | CDKN2A | CKS2 |
MCM7 | MSH6 | MSH6 | MSH6 | TOP2A | CDKN2A |
ORC1 | RAD9A | MSH2 | MSH2 | RPA1 | RPA1 |
CDC6 | DNMT1 | ATR | ATR | TP53 | ASF1B |
CDT1 | MSH2 | BRCA1 | BRCA1 | TUBG1 | MCM10 |
CDKN1A | CHEK1 | TK1 | TK1 | MSH2 | RPA2 |
CCNB1 | BARD1 | CDK1 | CDK1 | ATR | ATR |
CDK1 | CDK6 | CCNB1 | CCNB1 | CHEK1 | ORC1 |
TUBG1 | LIG1 | CCNA1 | CCNA1 | CDK1 | CCNA1 |
LMNB1 | CDKN2A | ORC6 | ORC6 | CCNA1 | CDC7 |
CCNB2 | TP53 | MCM4 | MCM4 | CCND1 | MMS22L |
CCND1 | CDK4 | MCM6 | MCM6 | AURKA | CCND1 |
MCM2 | CCND3 | MCM7 | MCM7 | CDK2 | MCM6 |
MCM3 | CCND1 | MCM2 | MCM2 | RFC2 | CDK2 |
POLD1 POLD2 | CDK2 CDC6 | MCM3 ORC2 | MCM3 ORC2 | ||
RPA1 | CDKN1A | CDK2 | CDK2 | ||
PCNA | CCNB2 | CDC5L | CDC5L | ||
BRCA1 | CDK1 | TP53 | TP53 | ||
TUBB CDC5L | CCNB1 CDT1 | TUBB RRM2 | TUBB RRM2 | ||
BIRC5 | L3MBTL1 | ||||
CCND3 | |||||
CDK6 | |||||
MSH2 SMC4 |
JUN (39) | MYC (37) | TERF1 (20) | ATF2 (29) | NR3C1 (15) | JUNB (15) | CREB1 (16) | CEBPG (15) |
---|---|---|---|---|---|---|---|
JUN | WARS | HSP90AA1 | NR4A1 | SAT1 | SREBF2 | CEBPE | |
DDIT3 | HIF1A | PGMI | FOSL1 | MVP | DDIT3 | ZNF451 | DDIT3 |
TRAF2 CCL2 | HSP90AA1 | FOXJ3 | CEBPA | CLU | ATF3 | JUN | ATF2 |
FOSL1 | MCM2 | BATF3 | SMARCC1 | CCL2 | MYC | ATF7 | |
ATF3 TGIF1 JUNB | CEBPA | HMOX1 | JUN | CREB1 | SMAD4 | NR3C1 | BATF |
CTNNB1 | TBPL1 | ATF7 | POU2F1 | JUN | ATF7 | BATF3 | |
GSK3B | DDX39A | FOS | CEBPA | BATF | DR1 | CEBPA | |
DBP BATF MAFG | RUNX1 | ENO2 | CTNNB1 | FOS | MAFG | DLD | ATF3 |
SERPINH1 | ACAT2 | CEBPG | JUN | BATF3 | ETS1 | ATF5 | |
TCF12 | MVK | ATF3 | MAFF | MAFK | FOS | MAFK | |
BATF3 MAFK HIF1A | KDM5B | ZNF281 | ETS1 | ETS1 | ATF2 | NFIL3 | DBP |
HSPD1 | LDHA | DDIT3 | KMT2A | ATF7 | POU2F1 | FOS | |
NMI | GAPDH | BACH1 | RARA | FOSL1 | MTF2 | FOSL1 | |
HDAC9 CEBPE NFATC2 | CREB1 | TPI1 | BATF | NR3C2 | FOS | RFX3 | NFIL3 |
CDK6 | HSPH1 | JUNB | HSPD1 | ETS1 | ZNF436 | JUN | |
SMAD4 FOS ETS1 | CXCR4 | NR4A1 | SERPINH1 | ZNF92 | |||
TOP2A | PLOD2 | SMAD4 | |||||
NFYC | CASP7 | ||||||
ATF7 ATF2 FOSL1 | SMARCC1 | ACLY | CANX | ||||
HSPH1 | ALDOA | CD44 | |||||
PIM1 | NFYA | ||||||
ZNF281 | |||||||
CCT6A | HSPH1 | ||||||
HSP90AA1 CEBPA CEBPG | ETV3 | DLD | |||||
IDH3B | HSPD1 | ||||||
CTNNB1 GSK3B RUNX1 | GCDH | ALDOA | |||||
ACOT8 | TPI1 | ||||||
IKBKB NR3C1 STAT1 | ZNF121 | LDHA | |||||
NUP205 | GAPDH | ||||||
POU2F1 CXCR4 TOP2A | PTPN11 | S100A10 | |||||
IDH3G | ACADVL | ||||||
SSR1 | |||||||
LGALS1 | |||||||
NFYA MYC CREB1 | ERCC3 | ||||||
PLK1 | |||||||
GCLM TCF4 BTG1 | ADNP | ||||||
RBPJ |
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Lai, M.W.; Chow, N.; Checco, A.; Kunar, B.; Redmond, D.; Rafii, S.; Rabbany, S.Y. Systems Biology Analysis of Temporal Dynamics That Govern Endothelial Response to Cyclic Stretch. Biomolecules 2022, 12, 1837. https://doi.org/10.3390/biom12121837
Lai MW, Chow N, Checco A, Kunar B, Redmond D, Rafii S, Rabbany SY. Systems Biology Analysis of Temporal Dynamics That Govern Endothelial Response to Cyclic Stretch. Biomolecules. 2022; 12(12):1837. https://doi.org/10.3390/biom12121837
Chicago/Turabian StyleLai, Michael W., Nathan Chow, Antonio Checco, Balvir Kunar, David Redmond, Shahin Rafii, and Sina Y. Rabbany. 2022. "Systems Biology Analysis of Temporal Dynamics That Govern Endothelial Response to Cyclic Stretch" Biomolecules 12, no. 12: 1837. https://doi.org/10.3390/biom12121837