{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUnder metabolic stress, miR-4734 functions as a critical negative regulator in primary fibroblasts by limiting the upregulation of proinflammatory cytokines and endoplasmic reticulum stress-associated genes. It achieves this by restricting the ATF4- and IRE1-mediated transcriptional activation of these genes, primarily through direct targeting of NFKBIZ mRNA—a key transcriptional activator required for optimal expression of these inflammatory mediators. Inhibition of miR-4734 leads to an enhanced inflammatory gene response, while its overexpression dampens the induction of such genes, underscoring its regulatory role under stress conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe stress-specific action of miR-4734 suggests that it may serve as a potential therapeutic target for alleviating metabolic stress-induced pathologies, by attenuating the inflammatory response that contributes to disease progression. Its ability to modulate key stress and inflammatory pathways positions miR-4734 as a promising candidate for further research into treatments aimed at mitigating the harmful effects of prolonged metabolic challenges."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dan Michael, Ester Feldmesser, Chagay Gonen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-4734 conditionally suppresses ER stress-associated proinflammatory responses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1873-3468.14548"}], "href": "https://doi.org/10.1002/1873-3468.14548"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36445168"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36445168"}]}]}]}