{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe combined studies reveal the functions and regulatory mechanisms of two distinct proteins involved in diverse physiological processes. One group of investigations focuses on a membrane‐bound mast cell serine protease—known as transmembrane tryptase (TMT) or tryptase γ, with its gene designated TPSG1—which is uniquely stored with its 18‐residue propeptide intact even after proteolytic activation. Upon mast cell degranulation, TPSG1 relocates to the plasma membrane where it acts as an exocytosed mediator that, despite its rapid inactivation by plasma serpins, induces airway hyperresponsiveness by triggering interleukin‑13 production and activating an IL‑13/IL‑4Rα/STAT6‑dependent pathway. In a related context, higher levels of tryptase in peritumoral tissues have been associated with breast cancer progression where its activity promotes cancer cell invasion and migration via activation of matrix metalloproteinase‑2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA second series of studies addresses the role of amelotin (AMTN), a secreted protein predominantly expressed during the maturation stage of enamel formation that directly promotes hydroxyapatite mineralization. Recombinant AMTN has been shown to stimulate HA precipitation and to bind the forming enamel matrix with an affinity comparable to amelogenin. Moreover, overexpression or mutation of AMTN in various animal models results in defective or unregulated enamel mineralization, establishing a critical role for AMTN in the formation of a compact, aprismatic enamel surface layer. In addition, AMTN is a bona fide component of the specialized basal lamina involved in epithelial-to-tooth adhesion, interacting with other extracellular proteins such as ODAM and SCPPPQ1 to structurally organize this matrix."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther investigations into the regulation of AMTN expression have demonstrated that its transcriptional levels are modulated in response to various inflammatory and developmental signals. Elevated AMTN mRNA and protein levels in gingival cells can be induced by proinflammatory cytokines such as IL‑1β, TNF‑α, and TGF‑β1, with key roles for transcription factors including Smad3, C/EBP, YY1, and Runx2. These studies highlight a complex regulatory network where positive signals (e.g., cytokine stimulation and Runx2/Cbfβ binding) enhance AMTN transcription, while factors such as Bax expression during apoptosis can downregulate TGF‑β1-induced AMTN expression. Such dynamic regulation underscores AMTN’s involvement not only in enamel maturation but also in the response to gingival inflammation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Guang W Wong, Paul S Foster, Shinsuke Yasuda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biochemical and functional characterization of human transmembrane tryptase (TMT)/tryptase gamma. TMT is an exocytosed mast cell protease that induces airway hyperresponsiveness in vivo via an interleukin-13/interleukin-4 receptor alpha/signal transducer and activator of transcription (STAT) 6-dependent pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M205868200"}], "href": "https://doi.org/10.1074/jbc.M205868200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12194977"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12194977"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Meng Xiang, Yiping Gu, Fengdi Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mast cell tryptase promotes breast cancer migration and invasion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or_00000676"}], "href": "https://doi.org/10.3892/or_00000676"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20126998"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20126998"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nastaran Abbarin, Symone San Miguel, James Holcroft, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The enamel protein amelotin is a promoter of hydroxyapatite mineralization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Bone Miner Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jbmr.2411"}], "href": "https://doi.org/10.1002/jbmr.2411"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25407797"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25407797"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Juliana Dos Santos Neves, Rima M Wazen, Shingo Kuroda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Odontogenic ameloblast-associated and amelotin are novel basal lamina components."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Histochem Cell Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00418-011-0901-4"}], "href": "https://doi.org/10.1007/s00418-011-0901-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22231912"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22231912"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Aurélien Fouillen, Juliana Dos Santos Neves, Charline Mary, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interactions of AMTN, ODAM and SCPPPQ1 proteins of a specialized basal lamina that attaches epithelial cells to tooth mineral."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep46683"}], "href": "https://doi.org/10.1038/srep46683"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28436474"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28436474"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Claire E L Smith, Gina Murillo, Steven J Brookes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deletion of amelotin exons 3-6 is associated with amelogenesis imperfecta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddw203"}], "href": "https://doi.org/10.1093/hmg/ddw203"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27412008"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27412008"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yan Sun, Juan-juan Zhang, Ting-ting Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Preparation and characterization of anti-Amelotin polyclonal antibody]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi (2009)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19351503"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19351503"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yohei Nakayama, Hideki Takai, Sari Matsui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional regulation of amelotin gene by proinflammatory cytokines in gingival fibroblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Connect Tissue Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3109/03008207.2014.923848"}], "href": "https://doi.org/10.3109/03008207.2014.923848"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25158173"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25158173"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yohei Nakayama, Sari Matsui, Keisuke Noda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Amelotin gene expression is temporarily being upregulated at the initiation of apoptosis induced by TGFβ1 in mouse gingival epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Apoptosis (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10495-016-1279-5"}], "href": "https://doi.org/10.1007/s10495-016-1279-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27502207"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27502207"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Keisuke Noda, Mizuho Yamazaki, Yasunobu Iwai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IL-1β and TNF-α regulate mouse amelotin gene transcription in gingival epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Oral Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2334/josnusd.17-0388"}], "href": "https://doi.org/10.2334/josnusd.17-0388"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30158339"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30158339"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Xiaoying Liu, Yumin Wang, Li Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Combination of Runx2 and Cbfβ upregulates Amelotin gene expression in ameloblasts by directly interacting with cis‑enhancers during amelogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2018.8564"}], "href": "https://doi.org/10.3892/mmr.2018.8564"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29436627"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29436627"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Yohei Nakayama, Sari Matsui, Keisuke Noda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TGFβ1-induced Amelotin gene expression is downregulated by Bax expression in mouse gingival epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Oral Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2334/josnusd.17-0271"}], "href": "https://doi.org/10.2334/josnusd.17-0271"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29657250"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29657250"}]}]}]}