{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough the query mentions MIR4501, none of the provided abstracts discuss this microRNA. Instead, they collectively focus on glomulin (GLMN), a protein that plays dual roles in vascular biology and in regulating innate immune responses. In murine development, GLMN is robustly expressed in vascular smooth muscle cells and the walls of large and smaller vessels, suggesting it is crucial for blood vessel development and maintenance. Mutations in the glomulin gene have been linked to glomuvenous malformations, highlighting its significance in vascular integrity and differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of the innate immune response, GLMN functions as an important negative regulator of inflammasome activation. Under normal conditions, GLMN interacts with cellular inhibitor of apoptosis proteins (cIAP1 and cIAP2) by binding specifically to their RING domains, thereby restraining their E3 ubiquitin ligase activities. This control mechanism helps to prevent excess inflammasome activation and subsequent pyroptotic cell death in macrophages."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nHowever, during bacterial infections such as those caused by Shigella, the pathogen deploys the IpaH7.8 E3 ubiquitin ligase effector to target GLMN for ubiquitination and proteasomal degradation. The removal of GLMN’s inhibitory action on cIAP-mediated pathways enhances inflammasome activation, promoting caspase-1-mediated pyroptotic cell death of macrophages. This bacterial strategy not only facilitates immune cell elimination but also drives severe inflammatory responses, underscoring GLMN’s critical role as a checkpoint in inflammasome signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Brendan A S McIntyre, Pascal Brouillard, Virginie Aerts, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glomulin is predominantly expressed in vascular smooth muscle cells in the embryonic and adult mouse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene Expr Patterns (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.modgep.2003.09.007"}], "href": "https://doi.org/10.1016/j.modgep.2003.09.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15053987"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15053987"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Shiho Suzuki, Hitomi Mimuro, Minsoo Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Shigella IpaH7.8 E3 ubiquitin ligase targets glomulin and activates inflammasomes to demolish macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1324021111"}], "href": "https://doi.org/10.1073/pnas.1324021111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25246571"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25246571"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shiho Suzuki, Toshihiko Suzuki, Hitomi Mimuro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Shigella hijacks the glomulin-cIAPs-inflammasome axis to promote inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embr.201643841"}], "href": "https://doi.org/10.15252/embr.201643841"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29191979"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29191979"}]}]}]}