Global Transcriptional Profiling Reveals Novel Autocrine Functions of Interleukin 6 in Human Vascular Endothelial Cells

Journal article

Background. Our earlier works showed the quick vascularization of mouse skin grafted Bombyx mori 3D silk fibroin nonwoven scaffolds (3D-SFnws) and the release of exosomes enriched in angiogenic/growth factors (AGFs) from in vitro 3D-SFnws-stuck human dermal fibroblasts (HDFs). Here, we explored whether coronary artery adult human smooth muscle cells (AHSMCs) also release AGFs-enriched exosomes when cultured on 3D-SFnws in vitro. Methods. Media with exosome-depleted FBS served for AHSMCs and human endothelial cells (HECs) cultures on 3D-SFnws or polystyrene. Biochemical methods and double-antibody arrays assessed cell growth, metabolism, and intracellular TGF-β and NF-κB signalling pathways activation. AGFs conveyed by CD9+/CD81+ exosomes released from AHSMCs were double-antibody array analysed and their angiogenic power evaluated on HECs in vitro. Results. AHSMCs grew and consumed D-glucose more intensely and showed a stronger phosphorylation/activation of TAK-1, SMAD-1/-2/-4/-5, ATF-2, c-JUN, ATM, CREB, and an IκBα phosphorylation/inactivation on SFnws vs. polystyrene, consistent overall with a proliferative/secretory phenotype. SFnws-stuck AHSMCs also released exosomes richer in IL-1α/-2/-4/-6/-8; bFGF; GM-CSF; and GRO-α/-β/-γ, which strongly stimulated HECs’ growth, migration, and tubes/nodes assembly in vitro. Conclusions. Altogether, the intensified AGFs exosomal release from 3D-SFnws-attached AHSMCs and HDFs could advance grafts’ colonization, vascularization, and take in vivo—noteworthy assets for prospective clinical applications

Authors: Ljungberg, LU; Zegeye, MM; Kardeby, C; Fälker, K; Repsilber, D

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Mediators of Inflammation
• Volume: 2020
• Pages: 1-12
• Publication date: 2020-04-28
• DOI: 10.1155/2020/4623107
• EISSN: 1466-1861
• ISSN: 0962-9351
• Language: English
• Keywords: Autocrine signalling; Biochemistry; Paracrine signalling; Cell culture; Cell biology; Gene knockdown; Receptor; Immunology; Genetics; Cytokine; Interleukin 6; Biology