Transcriptome Analysis of Hypoxic Lymphatic Endothelial Cells Indicates Their Potential to Contribute to Extracellular Matrix Rearrangement

Cells

Sonja Schwoch¹  Jörg Wilting¹  Christina Zelent¹  Jürgen Becker¹  Gabriela Salinas²  Maren Sitte² 

[1] Affiliation Department of Anatomy and Cell Biology, University Medical School Göttingen, 37075 Göttingen, Germany;Affiliation NGS-Integrative Genomics Core Unit (NIG), Institute of Human Genetics, University Medical Center Göttingen, 37075 Göttingen, Germany;

关键词: hypoxia;    extracellular matrix;    hyaluronan;    collagen;    fibrillogenesis;    elastin;   

DOI  :  10.3390/cells10051008

来源: DOAJ

【 摘 要 】

Lymphedema (LE) affects millions of people worldwide. It is a chronic progressive disease with massive development of fibrosclerosis when untreated. There is no pharmacological treatment of lymphedema. The disease is associated with swelling of the interstitium of the affected organ, mostly arm or leg, impressive development of adipose tissue, fibrosis and sclerosis with accumulation of huge amounts of collagen, and Papillomatosis cutis. Malnutrition and reduced oxygenation of the affected tissues is a hallmark of lymphedema. Here, we investigated if the hypoxia of lymphatic endothelial cells (LECs) might contribute to fibrosis. We applied RNASeq and qPCR to study the concordant changes of the exome of three human foreskin-derived LEC isolates after 4 days of hypoxia (1% O₂) vs. normoxia (21% O₂). Of the approximately 16,000 genes expressed in LECs, 162 (1%) were up- or down-regulated by hypoxia. Of these, 21 genes have important functions in the production or modification of the extracellular matrix (ECM). In addition to the down-regulation of elastin, we found up-regulation of druggable enzymes and regulators such as the long non-coding RNA H19, inter-alpha-trypsin inhibitor heavy chain family member 5 (ITIH5), lysyl-oxidase (LOX), prolyl 4-hydroxylase subunit alpha 1 (P4HA1), procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2), and others that are discussed in the paper. Initial lymphatics do not produce a continuous basement membrane; however, our study shows that hypoxic LECs have an unexpectedly high ability to alter the ECM.

【 授权许可】

Unknown