A characteristic feature of plants is their ability to produce a vast array of metabolites, a trait shaped by their evolution into sessile organisms. Over the past three decades, I have contributed to the development of phytochemical genomics, a field that emerged during the genomic era. Our research group established advanced analytical platforms for plant metabolomics by integrating state-of-the-art instruments with informatics tools. By combining genomics, transcriptomics, and metabolomics, we uncovered novel gene functions and identified new metabolites and gene-metabolite networks. Our study encompassed a broad spectrum of metabolites ranging from primary products, such as amino acids, sulfur-containing compounds, and lipids, to specialized (secondary) compounds, including flavonoids, alkaloids, and terpenoids. Initially, our focus was on the model plant Arabidopsis thaliana; however, we later included crops such as rice and tomato, as well as medicinal plants. This review highlights the key aspects of my research journey.
{"title":"Development of phytochemical genomics: From decoding metabolome to functional genomics and biotechnology of plant metabolism.","authors":"Kazuki Saito","doi":"10.2183/pjab.101.030","DOIUrl":"10.2183/pjab.101.030","url":null,"abstract":"<p><p>A characteristic feature of plants is their ability to produce a vast array of metabolites, a trait shaped by their evolution into sessile organisms. Over the past three decades, I have contributed to the development of phytochemical genomics, a field that emerged during the genomic era. Our research group established advanced analytical platforms for plant metabolomics by integrating state-of-the-art instruments with informatics tools. By combining genomics, transcriptomics, and metabolomics, we uncovered novel gene functions and identified new metabolites and gene-metabolite networks. Our study encompassed a broad spectrum of metabolites ranging from primary products, such as amino acids, sulfur-containing compounds, and lipids, to specialized (secondary) compounds, including flavonoids, alkaloids, and terpenoids. Initially, our focus was on the model plant Arabidopsis thaliana; however, we later included crops such as rice and tomato, as well as medicinal plants. This review highlights the key aspects of my research journey.</p>","PeriodicalId":20707,"journal":{"name":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","volume":"101 8","pages":"445-484"},"PeriodicalIF":4.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12674995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study explored the relationship between fall patterns and fall-related fractures in older adults. A cross-sectional survey was conducted among community-dwelling older adults in Maibara City, Japan, focusing on falls over the past three years. Among the 1,695 reported falls, 176 fractures occurred in 120 individuals. Backward or straight-down and sideways falls were more likely to result in fractures compared to forward falls, with odds ratios (95% confidence interval) of 3.23 (2.08-5.02) and 3.68 (2.35-5.76), respectively. Falls triggered by slipping or loss of balance had higher fracture rates than those triggered by tripping. Specific fall patterns were associated with particular fractures, such as forearm and patella fractures from forward falls, spine fractures from backward or straight-down falls, and hip fractures from sideways falls. We conclude that the fracture risk varies significantly based on fall patterns, providing insights for enhancing fall prevention strategies.
{"title":"Relationship between typical fall patterns and fall-related fractures in older Japanese adults.","authors":"Minoru Yamada, Yusuke Terao, Iwao Kojima, Shu Tanaka, Hiroki Saegusa, Miho Nanbu, Shiho Soma, Hiroki Matsumoto, Masaya Saito, Kohei Okawa, Naoto Haga, Hidenori Arai","doi":"10.2183/pjab.101.004","DOIUrl":"10.2183/pjab.101.004","url":null,"abstract":"<p><p>This study explored the relationship between fall patterns and fall-related fractures in older adults. A cross-sectional survey was conducted among community-dwelling older adults in Maibara City, Japan, focusing on falls over the past three years. Among the 1,695 reported falls, 176 fractures occurred in 120 individuals. Backward or straight-down and sideways falls were more likely to result in fractures compared to forward falls, with odds ratios (95% confidence interval) of 3.23 (2.08-5.02) and 3.68 (2.35-5.76), respectively. Falls triggered by slipping or loss of balance had higher fracture rates than those triggered by tripping. Specific fall patterns were associated with particular fractures, such as forearm and patella fractures from forward falls, spine fractures from backward or straight-down falls, and hip fractures from sideways falls. We conclude that the fracture risk varies significantly based on fall patterns, providing insights for enhancing fall prevention strategies.</p>","PeriodicalId":20707,"journal":{"name":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","volume":"101 2","pages":"98-106"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Iron is an essential element for organisms, but its solubility in soil is often extremely low. Previously, plants were considered to take up iron only after its reduction to ferrous ions. Takagi reported that oat and rice secrete chelating substances that solubilize ferric iron in the rhizosphere for efficient iron uptake. In 1978, Takemoto et al. reported the chemical structure of an iron-chelating compound secreted from barley roots, designated as mugineic acid. Mugineic acid and its derivatives, collectively known as mugineic acid family phytosiderophores (MAs), chelate ferric iron using octahedral hexacoordination. The specific iron uptake system by MAs in graminaceous plants was later classified by Römheld and Marschner as Strategy II, in contrast to Strategy I for reduction-based iron uptake by non-graminaceous plants. Further studies on MAs by Japanese researchers led to the identification of their biosynthetic pathways, corresponding enzymes and encoding genes, their regulation mechanisms, and the production of iron deficiency-tolerant and iron-rich crops.
铁是生物必需的元素,但它在土壤中的溶解度往往极低。以前,人们认为植物只有在铁还原为亚铁离子后才会吸收铁。Takagi报道说,燕麦和水稻分泌的螯合物质可以溶解根际的铁,从而有效地吸收铁。1978年,Takemoto等人报道了大麦根分泌的一种铁螯合化合物的化学结构,称为mugineic acid。Mugineic acid及其衍生物,统称Mugineic acid family phytosiderophores (MAs),通过八面体六配位螯合铁。后来,Römheld和Marschner将禾本科植物中MAs的特定铁吸收系统归类为策略II,而非禾本科植物的还原性铁吸收系统则为策略I。日本研究人员进一步研究了MAs的生物合成途径、相应的酶和编码基因及其调控机制,并生产出耐缺铁和富铁作物。
{"title":"Structural determination of mugineic acid, an iron(III)-chelating substance secreted from graminaceous plants for efficient iron uptake.","authors":"Takanori Kobayashi, Naoko K Nishizawa","doi":"10.2183/pjab.101.007","DOIUrl":"10.2183/pjab.101.007","url":null,"abstract":"<p><p>Iron is an essential element for organisms, but its solubility in soil is often extremely low. Previously, plants were considered to take up iron only after its reduction to ferrous ions. Takagi reported that oat and rice secrete chelating substances that solubilize ferric iron in the rhizosphere for efficient iron uptake. In 1978, Takemoto et al. reported the chemical structure of an iron-chelating compound secreted from barley roots, designated as mugineic acid. Mugineic acid and its derivatives, collectively known as mugineic acid family phytosiderophores (MAs), chelate ferric iron using octahedral hexacoordination. The specific iron uptake system by MAs in graminaceous plants was later classified by Römheld and Marschner as Strategy II, in contrast to Strategy I for reduction-based iron uptake by non-graminaceous plants. Further studies on MAs by Japanese researchers led to the identification of their biosynthetic pathways, corresponding enzymes and encoding genes, their regulation mechanisms, and the production of iron deficiency-tolerant and iron-rich crops.</p>","PeriodicalId":20707,"journal":{"name":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","volume":"101 2","pages":"55-67"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In 1962, Yoshihide Kozai reported his findings on the secular dynamics of asteroids moving in orbits with high inclination and eccentricity. In contrast to the classic understanding of the stability of planetary motion in the solar system, Kozai showed that asteroids can significantly change their orbital shape over a long timescale in an oscillatory manner between nearly circular orbits and highly elliptic orbits. An anti-correlated variation between orbital inclination and eccentricity characterizes this oscillation. The importance of Kozai's work in understanding the dynamical evolution of various systems was recognized decades later, including the fields of irregular satellites of planets, Oort Cloud, extrasolar planets, binary star systems, type Ia supernovae, planet climate, merging black hole systems, and so on.
{"title":"Re-recognized universality of Kozai oscillation on three-body dynamics.","authors":"Masanori Iye, Takashi Ito","doi":"10.2183/pjab.101.012","DOIUrl":"10.2183/pjab.101.012","url":null,"abstract":"<p><p>In 1962, Yoshihide Kozai reported his findings on the secular dynamics of asteroids moving in orbits with high inclination and eccentricity. In contrast to the classic understanding of the stability of planetary motion in the solar system, Kozai showed that asteroids can significantly change their orbital shape over a long timescale in an oscillatory manner between nearly circular orbits and highly elliptic orbits. An anti-correlated variation between orbital inclination and eccentricity characterizes this oscillation. The importance of Kozai's work in understanding the dynamical evolution of various systems was recognized decades later, including the fields of irregular satellites of planets, Oort Cloud, extrasolar planets, binary star systems, type Ia supernovae, planet climate, merging black hole systems, and so on.</p>","PeriodicalId":20707,"journal":{"name":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","volume":"101 3","pages":"143-176"},"PeriodicalIF":4.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sunlight-driven overall water splitting using particulate photocatalysts is of growing interest as a means of producing green hydrogen from water, because systems based on particulate photocatalysts can be spread over large areas using potentially inexpensive processes. Since the first reports on photocatalytic water splitting in 1980, a variety of materials have been developed. Alongside material development, systems designed for the practical implementation of solar hydrogen production technologies using particulate photocatalysts have recently emerged. This review highlights developments in photocatalyst research and examines the current progress in system design for the large-scale production of solar hydrogen (green hydrogen) based on these materials. Such technology represents a crucial solution in the pursuit of a carbon-neutral society-one of the most urgent global challenges.
{"title":"Particulate photocatalysts for water splitting to produce green hydrogen on a large scale.","authors":"Kazunari Domen","doi":"10.2183/pjab.101.035","DOIUrl":"10.2183/pjab.101.035","url":null,"abstract":"<p><p>Sunlight-driven overall water splitting using particulate photocatalysts is of growing interest as a means of producing green hydrogen from water, because systems based on particulate photocatalysts can be spread over large areas using potentially inexpensive processes. Since the first reports on photocatalytic water splitting in 1980, a variety of materials have been developed. Alongside material development, systems designed for the practical implementation of solar hydrogen production technologies using particulate photocatalysts have recently emerged. This review highlights developments in photocatalyst research and examines the current progress in system design for the large-scale production of solar hydrogen (green hydrogen) based on these materials. Such technology represents a crucial solution in the pursuit of a carbon-neutral society-one of the most urgent global challenges.</p>","PeriodicalId":20707,"journal":{"name":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","volume":"101 9","pages":"564-586"},"PeriodicalIF":4.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12709058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145506625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emil Fischer was a pioneer in peptide chemistry, striving to elucidate the chemical nature of peptides and proteins. In 1901, he and his colleague published the first paper on the subject. Since then, peptide chemistry has advanced steadily to the point that it is now possible to synthesize polypeptides, including enzymes. In addition, chemical synthesis is flexible and not constrained by the limitations of protein biosynthetic systems. Thus, proteins with various modifications, including post-translational modifications, can be synthesized. Current protein synthesis uses peptide thioesters synthesized by solid-phase methods as building blocks. This review will explain why peptide thioesters are utilized as building blocks for polypeptide synthesis and discuss the evolution of thioester preparation methods, as well as their applications in protein synthesis.
{"title":"Development of protein chemical synthesis using peptide thioester synthetic blocks.","authors":"Saburo Aimoto, Toru Kawakami, Hironobu Hojo","doi":"10.2183/pjab.101.034","DOIUrl":"https://doi.org/10.2183/pjab.101.034","url":null,"abstract":"<p><p>Emil Fischer was a pioneer in peptide chemistry, striving to elucidate the chemical nature of peptides and proteins. In 1901, he and his colleague published the first paper on the subject. Since then, peptide chemistry has advanced steadily to the point that it is now possible to synthesize polypeptides, including enzymes. In addition, chemical synthesis is flexible and not constrained by the limitations of protein biosynthetic systems. Thus, proteins with various modifications, including post-translational modifications, can be synthesized. Current protein synthesis uses peptide thioesters synthesized by solid-phase methods as building blocks. This review will explain why peptide thioesters are utilized as building blocks for polypeptide synthesis and discuss the evolution of thioester preparation methods, as well as their applications in protein synthesis.</p>","PeriodicalId":20707,"journal":{"name":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","volume":"101 10","pages":"622-647"},"PeriodicalIF":4.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145725789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Photoredox catalysis, which facilitates organic transformations under visible-light irradiation, including sunlight, has garnered considerable attention as a cornerstone of green chemistry. Since the early days of this field around 2010, the author's group has made substantial contributions to its advancement. This review article provides a concise overview of the history and fundamental principles of photoredox catalysis, along with highlights of the achievements by the author's group. Although colorless organic compounds cannot be directly activated by visible light, photo-excited colored catalysts, with their two half-occupied frontier orbitals, play dual roles via electron transfer processes with organic substrates. The hole in the lower-energy orbital functions as a single-electron oxidant, whereas the electron in the higher-energy orbital acts as a single-electron reductant, enabling the formation of reactive radical intermediates from diverse organic compounds, including colorless ones. The discussion will focus on the key transformations developed by the author's group, including bimetallic photocatalysis, fluoroalkylation, and catalysis in aqueous media.
{"title":"Dawn of photoredox catalysis.","authors":"Munetaka Akita","doi":"10.2183/pjab.101.019","DOIUrl":"10.2183/pjab.101.019","url":null,"abstract":"<p><p>Photoredox catalysis, which facilitates organic transformations under visible-light irradiation, including sunlight, has garnered considerable attention as a cornerstone of green chemistry. Since the early days of this field around 2010, the author's group has made substantial contributions to its advancement. This review article provides a concise overview of the history and fundamental principles of photoredox catalysis, along with highlights of the achievements by the author's group. Although colorless organic compounds cannot be directly activated by visible light, photo-excited colored catalysts, with their two half-occupied frontier orbitals, play dual roles via electron transfer processes with organic substrates. The hole in the lower-energy orbital functions as a single-electron oxidant, whereas the electron in the higher-energy orbital acts as a single-electron reductant, enabling the formation of reactive radical intermediates from diverse organic compounds, including colorless ones. The discussion will focus on the key transformations developed by the author's group, including bimetallic photocatalysis, fluoroalkylation, and catalysis in aqueous media.</p>","PeriodicalId":20707,"journal":{"name":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","volume":"101 5","pages":"274-301"},"PeriodicalIF":4.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In 2001, we launched the Hokkaido Study, the first prospective birth cohort study in Japan. We are currently tracking the effects of environmental chemicals, using a life course approach. The study examines life circumstances after birth, and the longest follow-up to date is 20 years of age. We have measured prenatal exposure to dioxins, organochlorine pesticides, per- and polyfluoroalkyl substances, plasticizers such as di(2-ethylhexyl) phthalate, and bisphenol A. Our findings have mostly revealed that increased exposure to these environmental chemicals is linked to increased risk of lower birth size, effects on thyroid and steroid hormones, adipokine levels, as well as disruption of neurodevelopment, including causing asthma and respiratory symptoms. However, it should be noted that our findings also include protective or null findings, which may be due to low chemical concentrations or differences in prenatal or postnatal exposure. We would like to emphasize the importance of long-term continuation of the cohort, effective utilization of the data, and application of the results to environmental and health policies.
{"title":"The potential health risks of exposure to environmental chemicals - Global implications for future generations.","authors":"Reiko Kishi, Atsuko Ikeda, Rahel Mesfin Ketema","doi":"10.2183/pjab.101.015","DOIUrl":"10.2183/pjab.101.015","url":null,"abstract":"<p><p>In 2001, we launched the Hokkaido Study, the first prospective birth cohort study in Japan. We are currently tracking the effects of environmental chemicals, using a life course approach. The study examines life circumstances after birth, and the longest follow-up to date is 20 years of age. We have measured prenatal exposure to dioxins, organochlorine pesticides, per- and polyfluoroalkyl substances, plasticizers such as di(2-ethylhexyl) phthalate, and bisphenol A. Our findings have mostly revealed that increased exposure to these environmental chemicals is linked to increased risk of lower birth size, effects on thyroid and steroid hormones, adipokine levels, as well as disruption of neurodevelopment, including causing asthma and respiratory symptoms. However, it should be noted that our findings also include protective or null findings, which may be due to low chemical concentrations or differences in prenatal or postnatal exposure. We would like to emphasize the importance of long-term continuation of the cohort, effective utilization of the data, and application of the results to environmental and health policies.</p>","PeriodicalId":20707,"journal":{"name":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","volume":"101 4","pages":"197-215"},"PeriodicalIF":4.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell proliferation is a fundamental characteristic of organisms, driven by the holistic functions of multiple proteins encoded in the genome. However, the individual contributions of thousands of genes and the millions of protein molecules they express to cell proliferation are still not fully understood, even in simple eukaryotes. Here, we present a genome-wide translation map of cells during proliferation in the unicellular alga Cyanidioschyzon merolae, based on the sequencing of ribosome-protected messenger RNA fragments. Ribosome profiling has revealed both qualitative and quantitative changes in protein translation for each gene during cell division, driven by the large-scale reallocation of ribosomes. Comparisons of ribosome footprints from non-dividing and dividing cells allowed the identification of proteins involved in cell proliferation. Given that in vivo experiments on two selected candidate proteins identified a division-phase-specific mitochondrial nucleoid protein and a mitochondrial division protein, further analysis of the candidate proteins may offer key insights into the comprehensive mechanism that facilitate cell and organelle proliferation.
{"title":"Genome-wide changes of protein translation levels for cell and organelle proliferation in a simple unicellular alga.","authors":"Yuko Mogi, Yoshitaka Matsuo, Yuiki Kondo, Tetsuya Higashiyama, Toshifumi Inada, Yamato Yoshida","doi":"10.2183/pjab.101.002","DOIUrl":"10.2183/pjab.101.002","url":null,"abstract":"<p><p>Cell proliferation is a fundamental characteristic of organisms, driven by the holistic functions of multiple proteins encoded in the genome. However, the individual contributions of thousands of genes and the millions of protein molecules they express to cell proliferation are still not fully understood, even in simple eukaryotes. Here, we present a genome-wide translation map of cells during proliferation in the unicellular alga Cyanidioschyzon merolae, based on the sequencing of ribosome-protected messenger RNA fragments. Ribosome profiling has revealed both qualitative and quantitative changes in protein translation for each gene during cell division, driven by the large-scale reallocation of ribosomes. Comparisons of ribosome footprints from non-dividing and dividing cells allowed the identification of proteins involved in cell proliferation. Given that in vivo experiments on two selected candidate proteins identified a division-phase-specific mitochondrial nucleoid protein and a mitochondrial division protein, further analysis of the candidate proteins may offer key insights into the comprehensive mechanism that facilitate cell and organelle proliferation.</p>","PeriodicalId":20707,"journal":{"name":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","volume":"101 1","pages":"41-53"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The biological activity of hyaluronan (HA), a major component of the extracellular matrix in vertebrate tissues, depends on its molecular weight, and thus its degradation is a critical process for HA biological functions. Here, we review the characteristics of newly discovered proteins essential for HA degradation, hyaluronan-binding protein involved in hyaluronan depolymerization (HYBID), also known as cell migration inducing hyaluronidase 1 (CEMIP) and KIAA1199, and transmembrane protein-2 (TMEM2; alias CEMIP2). Human and mouse forms of HYBID exert their HA-degrading activity in special microenvironments including recycling endosomes. Mouse TMEM2 functions as a cell-surface hyaluronidase for HA turnover in local tissues, lymph nodes, and the liver. In contrast, the role of human TMEM2 in HA degradation is the subject of much debate. HYBID expression is upregulated by proinflammatory factors such as histamine and interleukin-6 and downregulated by transforming growth factor-β. HYBID is involved in physiological HA turnover in human skin and joint tissues and plays an important role in their pathological destruction by accelerating HA degradation.
{"title":"New molecules indispensable for hyaluronan degradation, HYBID (CEMIP/KIAA1199) and TMEM2 (CEMIP2): Differential roles in physiological and pathological non-neoplastic conditions.","authors":"Hiroyuki Yoshida, Shintaro Inoue, Yasunori Okada","doi":"10.2183/pjab.101.021","DOIUrl":"10.2183/pjab.101.021","url":null,"abstract":"<p><p>The biological activity of hyaluronan (HA), a major component of the extracellular matrix in vertebrate tissues, depends on its molecular weight, and thus its degradation is a critical process for HA biological functions. Here, we review the characteristics of newly discovered proteins essential for HA degradation, hyaluronan-binding protein involved in hyaluronan depolymerization (HYBID), also known as cell migration inducing hyaluronidase 1 (CEMIP) and KIAA1199, and transmembrane protein-2 (TMEM2; alias CEMIP2). Human and mouse forms of HYBID exert their HA-degrading activity in special microenvironments including recycling endosomes. Mouse TMEM2 functions as a cell-surface hyaluronidase for HA turnover in local tissues, lymph nodes, and the liver. In contrast, the role of human TMEM2 in HA degradation is the subject of much debate. HYBID expression is upregulated by proinflammatory factors such as histamine and interleukin-6 and downregulated by transforming growth factor-β. HYBID is involved in physiological HA turnover in human skin and joint tissues and plays an important role in their pathological destruction by accelerating HA degradation.</p>","PeriodicalId":20707,"journal":{"name":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","volume":"101 6","pages":"317-338"},"PeriodicalIF":4.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}