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However, the precise mechanism underlying the decision between cell survival and death remains unclear. Here, we demonstrate that Engulfment and Cell Motility 1 (ELMO1), an intracellular protein that facilitates cytoskeleton rearrangement through activation of Rac family small GTPase 1 (RAC1), is involved in the Toll-like receptor 3 (TLR3)-induced apoptosis in human umbilical vein endothelial cells. RNA sequencing of cells treated with ELMO1-targeting siRNA (siELMO1) revealed that knockdown of ELMO1 increased the transcripts of extracellular matrix genes including\n                    <jats:italic>COL5A1<\/jats:italic>\n                    and decreased the expression of cell cycle and DNA replication-related genes such as\n                    <jats:italic>CCND1<\/jats:italic>\n                    and\n                    <jats:italic>CDK1<\/jats:italic>\n                    . These siELMO1 treated cells also showed G1\/S cell cycle arrest. When stimulated with polyinosinic-polycytidylic acid (poly(I:C)), a TLR3 agonist, inflammatory cytokines and chemokines such as\n                    <jats:italic>CXCL8<\/jats:italic>\n                    and\n                    <jats:italic>IL6<\/jats:italic>\n                    robustly increased in Mock-treated cells, while siNT (non-targeting) cells underwent massive cell death and showed reduced inflammatory responses, reflecting apoptosis-inducing effects of sequential TLR3 activation by siRNA and poly(I:C). Strikingly, siELMO1 cells were resistant to the cell death, and restored inflammatory cytokine responses to the same level as Mock-treated cells. Mechanistically, apoptosis in siNT increased through the activation of caspase-8, whereas downregulation of ELMO1 inhibited the cleavage of caspase-8. These results indicate that ELMO1 is involved in the regulation between survival or death in endothelial cells through the regulation of caspase-8 activity downstream of TLR3, suggesting the importance of the ELMO1 in cell proliferation as well as susceptibility to poly(I:C)-induced apoptosis.\n                  <\/jats:p>","DOI":"10.1038\/s41419-025-08341-1","type":"journal-article","created":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T12:55:06Z","timestamp":1766235306000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Downregulation of Engulfment and cell motility 1 (Elmo1) induces quiescence and resistance to poly(I:C)-induced apoptosis in endothelial cells"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3415-9135","authenticated-orcid":false,"given":"Yukako","family":"Kayashima","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anshulika A.","family":"Deshmukh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Kiyokawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niroshani M. 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