{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T09:09:35Z","timestamp":1763975375812,"version":"3.45.0"},"reference-count":57,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T00:00:00Z","timestamp":1763769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, MEXT, Japan","award":["22K06587","25K09962"],"award-info":[{"award-number":["22K06587","25K09962"]}]},{"name":"J-GlycoNet cooperative network","award":["25C014"],"award-info":[{"award-number":["25C014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A chimeric protein of heparanase and Ig-Fc was designed as a novel tool to expand the detection of structurally heterogeneous heparan sulfate (HS) and related glycosaminoglycans. The whole mouse heparanase gene was combined with the gene segment encoding the mouse IgG1 hinge-Fc domain. A point mutation E335A was inserted to disable putative HS degradation activity. Chimeric proteins consisted of the latent form of the enzyme devoid of HS degradation activity. The chimeric proteins bound to heparin, N-desulfated heparin, and O-sulfated N-acetylheparosan. Their binding spectrum to glycosaminoglycans differed from that of anti-HS mAb 10E4. The chimeric proteins bound to Kato III and A549 cell lines. The binding was reduced by knocking down EXT1 gene expression. One of the chimeric proteins stained the epidermal cells in the hyperplastic spinous layer of inflamed atopic dermatitis skin and inflammatory cells in the dermis, which were not stained with mAb 10E4. The protein stained a polarized structure on the surface of monocytic U937 and THP1 cells. Similar polarized structures were observed with anti-syndecan-1 antibody staining. The chimeric protein and anti-syndecan-1 antibody precipitated similar sets of proteins that included syndecan-1 from the lysates of U937 cells. These novel chimeric proteins are useful to detect HS abundant in O-sulfation in histochemical, cytochemical, and biochemical studies.<\/jats:p>","DOI":"10.3390\/ijms262311293","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T09:02:07Z","timestamp":1763974927000},"page":"11293","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Chimeric Molecule of Heparanase and Ig-Fc Enables Histochemical and Cytochemical Detection of O-sulfated Heparan Sulfate"],"prefix":"10.3390","volume":"26","author":[{"given":"Jia","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Momoko","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryoya","family":"Baba","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sojiro","family":"Arakawa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arisa","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, 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School of Pharmacy and Pharmaceutical Sciences, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1086-1803","authenticated-orcid":false,"given":"Mayumi","family":"Komine","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke 329-0498, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Momo","family":"Shimekake","sequence":"additional","affiliation":[{"name":"Department of Clinical and Analytical Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Sciences, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2622-4825","authenticated-orcid":false,"given":"Kyohei","family":"Higashi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Analytical Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Sciences, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6171-3942","authenticated-orcid":false,"given":"Masao","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Peptidomics, Sasaki Institute, 2-2, Kandasurugadai, Chiyoda-ku, Tokyo 101-0062, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9126-0351","authenticated-orcid":false,"given":"Kazuki","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Peptidomics, Sasaki Institute, 2-2, Kandasurugadai, Chiyoda-ku, Tokyo 101-0062, Japan"},{"name":"Department of Oncopeptidomics, Tochigi Cancer Center, 4-9-13, Yonan, Utsunomiya 320-0834, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7687-6365","authenticated-orcid":false,"given":"Motowo","family":"Nakajima","sequence":"additional","affiliation":[{"name":"SBI Pharmaceuticals Co., Ltd., 1-6-1, Roppongi, Minato-ku, Tokyo 106-6019, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4709-3131","authenticated-orcid":false,"given":"Tatsuro","family":"Irimura","sequence":"additional","affiliation":[{"name":"Division of Glycobiologics, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan"},{"name":"Department of Breast Oncology, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, 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