Transcriptome Analysis of Hypoxic Lymphatic Endothelial Cells Indicates Their Potential to Contribute to Extracellular Matrix Rearrangement
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Immunocytology
2.3. Real-Time RT-PCR (qPCR)
2.4. Transcriptome and Bioinformatic Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ADAMTS6/15 | ADAM metallopeptidase with thrombospondin type 1 motif 6/15 |
ANGPTL4 | Angiopoietin-like 4 |
BEC | Blood vascular endothelial cell |
CDT | Comprehensive decongestive therapy |
CEMIP2 | Cell migration inducing hyaluronidase 2; also known as: transmembrane protein 2 |
CHST2 | Carbohydrate sulfotransferase 2 |
CP | Ceruloplasmin |
ECM | Extracellular matrix |
EGLN3 | Egl-9 family hypoxia inducible factor 3 (=PHD3) |
ELN | Elastin |
FBLN5 | Fibulin 5 |
FMOD | Fibromodulin |
H19 | Long non-coding RNA H19 |
HA | Hyaluronic acid |
HD-LEC | Human dermal lymphatic endothelial cells |
HIF | Hypoxia-inducible factor |
HMVEC | Human microvascular endothelial cell |
HTRA3 | HtrA serine peptidase 3 |
ITIH5 | Inter-alpha-trypsin inhibitor heavy chain family member 5 |
LE | Lymphedema |
LEC | Lymphatic endothelial cell |
lncRNA | Long non-coding RNA |
LOX | Lysyl-oxidase |
MMP1 | Matrix metalloproteinase 1 |
P4HA1 | Prolyl 4-hydroxylase subunit alpha 1 |
PHD | Prolyl hydroxylase |
PLOD2 | Procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 |
SLC2A3 | Solute carrier family 2 member 3 (= GLUT3) |
TGFB1/2/3 | Transforming growth factor-β1/2/3 |
TNS1 | Tensin-1 |
TNXB | Tenascin-XB |
VEGF-A | Vascular endothelial growth factor-A |
VWA1 | von Willebrand factor A domain containing 1 |
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Name | Fwd 5′–3′ | Rev 5′–3′ |
---|---|---|
ADAMTS15 | ACCTGAGTGGTTCATTGGGG | TCTCCTCCTCAGAAGGTCCG |
ADAMTS6 | ACCTGAGTGGTTCATTGGGG | TCTCCTCCTCAGAAGGTCCG |
CEMIP2 | TGGTCGCAAGCACAGACTAT | TGCAGGAACTGAGGGGTTTC |
CP | GAGAGGCCCTGAAGAAGAGC | TGATGGTGTCTCCCACCTCT |
ELN | CTTTCCCGGCTTTGGTGTCG | CCTGAGCTTCGGGGGAAATG |
FBLN5 | TCCTGCACCGACGGATATTG | GCTGGCAGTAACCATAGCGA |
FMOD | AACCAGCTGCAGAAGATCCC | GCAGAAGCTGCTGATGGAGA |
H19 | GCACCTTGGACATCTGGAGT | GCCTACTCCACACTCCTCAC |
HTRA3 | CATACGGATGCGGACGATCA | GAATTCGGCGCAACCTCTTG |
ITIH5 | GTGGGGTCGCAGGAAGAG | AACAGTCTGACTTGCCTCGG |
LOX | GGGTCTGAATCCCACCCTTG | AAAAACGGGGCTCAAATCACG |
MMP1 | CCAGGTATTGGAGGGGATGC | GTCCAAGAGAATGGCCGAGT |
P4HA1 | AGGATGAATGGGACAAGCCTC | GGGTCATGTACTGTAGCTCGG |
PLOD2 | GAGAAGCCCTCGAGCATCC | GGCTGACTGCATAAATCGATGG |
TGFB2 | ACAACACCCTCTGGCTCAGT | CTGTAGAAAGTGGGCGGGAT |
TGFB3 | ACCCAGGAAAACACCGAGTC | TTAGGGCAGACAGCCAGTTC |
TNS1 | CCATGTCTCTGGTGGGCAAA | TGGGAGGATTTGAGCTGTCC |
TNXB | TCTGTCAGGCAGGAAACGAC | AGGTAGCTCCTTCTCCAGGG |
VWA1 | TTGTGGACGTGGATGACCTG | CTGGACGTGATCTCCGTGG |
Gene Name | Chromos. | Strand | Gene type | Base Mean | Base Mean Ctrl | Base Mean Treat | log2 FC | qPCR FC ± SD | p Value | Padj |
---|---|---|---|---|---|---|---|---|---|---|
H19 | 11 | - | lncRNA | 1102.56 | 49.10 | 2156.03 | 4.54 | 19.9 ± 23 | 2.21 × 10−121 | 3.00 × 10−117 |
CP | 3 | - | prot_coding | 131.14 | 5.32 | 256.96 | 1.98 | 54.6 ± 7.7 | 9.70 × 10−13 | 2.86 × 10−10 |
ITIH5 | 10 | - | prot_coding | 149.79 | 43.16 | 256.41 | 1.69 | 5.7 ± 2.5 | 1.10 × 10−10 | 2.22 × 10−8 |
FBLN5 | 14 | - | prot_coding | 472.33 | 140.55 | 804.10 | 1.47 | 5.5 ± 6.0 | 1.19 × 10−8 | 1.64 × 10−6 |
FMOD | 1 | - | prot_coding | 3576.51 | 1724.37 | 5428.65 | 1.40 | 2.2 ± 2.1 | 2.23 × 10−19 | 2.33 × 10−16 |
MMP1 | 11 | - | prot_coding | 5844.68 | 2513.30 | 9176.05 | 1.35 | 1.9 ± 1.3 | 1.23 × 10−14 | 4.64 × 10−12 |
CHST2 | 3 | + | prot_coding | 1493.45 | 745.04 | 2241.85 | 1.24 | - | 1.30 × 10−9 | 2.13 × 10−7 |
HTRA3 | 4 | + | prot_coding | 183.02 | 87.13 | 278.90 | 1.22 | 7.5 ± 8.8 | 4.99 × 10−7 | 4.48 × 10−5 |
TNXB | 6 | - | prot_coding | 208.02 | 45.08 | 370.95 | 1.21 | 3.7 ± 4.8 | 9.67 × 10−6 | 6.07 × 10−4 |
TGFB2 | 1 | + | prot_coding | 2836.67 | 1540.02 | 4133.33 | 1.20 | 1.7 ± 1.0 | 3.40 × 10−11 | 7.56 × 10−9 |
PLOD2 | 3 | - | prot_coding | 9973.82 | 6024.54 | 13923.10 | 1.15 | 3.2 ± 0.6 | 2.78 × 10−20 | 3.14 × 10−17 |
TGFB3 | 14 | - | prot_coding | 106.46 | 40.28 | 172.64 | 1.15 | 7.0 ± 6.2 | 2.13 × 10−5 | 1.17 × 10−3 |
P4HA1 | 10 | - | prot_coding | 2797.71 | 1640.17 | 3955.25 | 1.15 | 1.6 ± 0.9 | 9.35 × 10−13 | 2.82 × 10−10 |
TNS1 | 2 | - | prot_coding | 6950.84 | 4073.20 | 9828.48 | 1.14 | 4.7 ± 1.7 | 7.92 × 10−7 | 6.59 × 10−5 |
CEMIP2 | 9 | - | prot_coding | 5188.67 | 2510.43 | 7866.90 | 1.14 | 4.1 ± 3.1 | 8.12 × 10−8 | 8.73 × 10−6 |
ADAMTS6 | 5 | - | prot_coding | 624.19 | 374.99 | 873.40 | 1.09 | 2.9 ± 0.5 | 2.73 × 10−10 | 5.13 × 10−8 |
LOX | 5 | - | prot_coding | 3001.85 | 1871.25 | 4132.45 | 1.04 | 3.9 ± 0.1 | 9.24 × 10−8 | 9.71 × 10−6 |
VWA1 | 1 | + | prot_coding | 687.79 | 877.41 | 498.16 | −1.02 | 0.9 ± 0.2 | 1.12 × 10−5 | 6.79 × 10−4 |
ADAMTS15 | 11 | + | prot_coding | 584.60 | 895.85 | 273.35 | −1.49 | 0.7 ± 0.3 | 1.22 × 10−11 | 3.00 × 10−9 |
ELN | 7 | + | prot_coding | 6210.97 | 965.37 | 2770.58 | −1.69 | 0.4 ± 0.4 | 2.26 × 10−31 | 6.14 × 10−28 |
Gene-Id | Gene-Symbol | Chromos. | Gene-Name | LEC5; 21% O2 | LEC6; 21% O2 | LEC7; 21% O2 | LEC5; 1% O2 | LEC6; 1% O2 | LEC7; 1% O2 |
---|---|---|---|---|---|---|---|---|---|
ENSG00000110799 | VWF | 12 | von Willebrand factor | 110,056 | 74,476 | 31,043 | 92,868 | 45,799 | 56,732 |
ENSG00000110800 | COL4A1 | 13 | Collagen IV alpha 1 chain | 40,704 | 48,506 | 74,087 | 49,831 | 39,451 | 66,389 |
ENSG00000110801 | COL4A2 | 13 | Collagen IV alpha 2 chain | 29,111 | 40,049 | 66,375 | 37,650 | 35,392 | 78,698 |
ENSG00000110802 | COL8A1 | 3 | Collagen VIII alpha 1 chain | 19,050 | 34,930 | 9414 | 16,103 | 17,801 | 10,441 |
ENSG00000110803 | COL18A1 | 21 | Collagen XVIII alpha 1 chain | 29,847 | 10,505 | 17,796 | 38,463 | 10,204 | 17,105 |
ENSG00000110804 | COL5A2 | 2 | Collagen V alpha 2 chain | 3820 | 3535 | 13,285 | 5904 | 3889 | 12,653 |
ENSG00000110805 | COL4A5 | X | Collagen IV alpha 5 chain | 2114 | 676 | 2081 | 2145 | 864 | 1977 |
ENSG00000110806 | COL6A2 | 21 | Collagen VI alpha 2 chain | 104 | 359 | 304 | 229 | 535 | 383 |
ENSG00000110807 | COL5A1 | 9 | Collagen V alpha 1 chain | 2250 | 306 | 3762 | 4098 | 458 | 6698 |
ENSG00000110808 | COL11A2 | 6 | Collagen XI alpha 2 chain | 41 | 155 | 46 | 48 | 87 | 38 |
ENSG00000110809 | FBN1 | 15 | Fibrillin 1 | 10,648 | 5180 | 3912 | 9795 | 7227 | 3071 |
ENSG00000110810 | LAMA4 | 6 | Laminin alpha 4 | 22,245 | 16,175 | 11,342 | 27,918 | 16,742 | 15,632 |
ENSG00000110811 | LAMA5 | 20 | Laminin alpha 5 | 2174 | 632 | 4070 | 2380 | 465 | 4739 |
ENSG00000110812 | LAMA3 | 18 | Laminin alpha 3 | 484 | 167 | 349 | 582 | 125 | 366 |
ENSG00000110813 | LAMB1 | 7 | Laminin beta 1 | 28,134 | 14,482 | 23,098 | 30,873 | 13,910 | 38,887 |
ENSG00000110814 | LAMB2 | 3 | Laminin beta 2 | 10,535 | 9591 | 4763 | 13,436 | 10,002 | 7752 |
ENSG00000110815 | HSPG2 | 1 | Perlecan | 50,132 | 24,772 | 30,919 | 37,175 | 14,955 | 39,144 |
ENSG00000110816 | FN1 | 2 | Fibronectin | 104,522 | 45,391 | 173,759 | 156,880 | 90,964 | 671,160 |
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Becker, J.; Schwoch, S.; Zelent, C.; Sitte, M.; Salinas, G.; Wilting, J. Transcriptome Analysis of Hypoxic Lymphatic Endothelial Cells Indicates Their Potential to Contribute to Extracellular Matrix Rearrangement. Cells 2021, 10, 1008. https://doi.org/10.3390/cells10051008
Becker J, Schwoch S, Zelent C, Sitte M, Salinas G, Wilting J. Transcriptome Analysis of Hypoxic Lymphatic Endothelial Cells Indicates Their Potential to Contribute to Extracellular Matrix Rearrangement. Cells. 2021; 10(5):1008. https://doi.org/10.3390/cells10051008
Chicago/Turabian StyleBecker, Jürgen, Sonja Schwoch, Christina Zelent, Maren Sitte, Gabriela Salinas, and Jörg Wilting. 2021. "Transcriptome Analysis of Hypoxic Lymphatic Endothelial Cells Indicates Their Potential to Contribute to Extracellular Matrix Rearrangement" Cells 10, no. 5: 1008. https://doi.org/10.3390/cells10051008