{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStudies in reproductive biology have uncovered the critical roles of proteolytic enzymes in ovarian and uterine function. For example, two related serine proteases—PRSS35 and PRSS23—have been identified as key regulators in follicular growth, ovulation, corpus luteum formation/regression, and even in early uterine remodeling during implantation. Their dynamic expression patterns in the ovary and periimplantation uterus highlight essential roles in tissue remodeling and reproductive physiology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn parallel, investigations into inflammatory and fibrotic disorders have demonstrated that disruptions in protease regulatory networks can contribute to pathological tissue remodeling. For instance, studies in a lupus nephritis model revealed that alterations of protease expression—together with other mediators—correlate with renal inflammation and fibrosis, underscoring the complexity of protease function beyond traditional reproductive roles."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast to these protease‐driven processes, recent work has highlighted the distinct function of thioesterase superfamily member 6 (THEM6) in breast cancer. THEM6, a lipid metabolism–related gene, is significantly overexpressed in breast invasive carcinoma compared with adjacent normal tissues, and its high expression correlates with poorer overall survival. Functional assays indicate that elevated THEM6 levels promote cancer cell proliferation, invasion, and cell cycle progression while inhibiting apoptosis. Moreover, THEM6 appears to modulate the tumor microenvironment by influencing macrophage recruitment and polarization—possibly through the regulation of CCL2 secretion—thereby contributing to tumor progression. These findings suggest that, unlike the proteolytic pathways governing reproductive tissue remodeling, THEM6 represents an independent oncogenic driver and a promising prognostic biomarker as well as therapeutic target in breast cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kei Miyakoshi, Melinda J Murphy, Richard R Yeoman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The identification of novel ovarian proteases through the use of genomic and bioinformatic methodologies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Reprod (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1095/biolreprod.106.052290"}], "href": "https://doi.org/10.1095/biolreprod.106.052290"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16870946"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16870946"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Patrik Wahlberg, Asa Nylander, Nina Ahlskog, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and localization of the serine proteases high-temperature requirement factor A1, serine protease 23, and serine protease 35 in the mouse ovary."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2007-1736"}], "href": "https://doi.org/10.1210/en.2007-1736"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18566130"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18566130"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Honglu Diao, Shuo Xiao, Rong Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct spatiotemporal expression of serine proteases Prss23 and Prss35 in periimplantation mouse uterus and dispensable function of Prss35 in fertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0056757"}], "href": "https://doi.org/10.1371/journal.pone.0056757"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23451081"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23451081"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yixia Li, Xiaorong Zhong, Feng Yang "}, {"type": "b", "children": [{"type": "t", "text": "Silencing HE4 alleviates the renal fibrosis in lupus nephritis mice by regulating the C3/MMPs/prss axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Naunyn Schmiedebergs Arch Pharmacol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00210-023-02883-x"}], "href": "https://doi.org/10.1007/s00210-023-02883-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38157023"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38157023"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xingjia Lu, Wenlin Chen, Gengzhou Tian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "THEM6 is a prognostic biomarker for breast cancer and is associated with immune infiltration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-023-49379-5"}], "href": "https://doi.org/10.1038/s41598-023-49379-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38081884"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38081884"}]}]}]}