caa a22 4500 606235361 CHVBK 20210128101242.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s11010-015-2495-y doi (NATIONALLICENCE)springer-10.1007/s11010-015-2495-y SVVYGLR motif of the thrombin-cleaved N-terminal osteopontin fragment enhances the synthesis of collagen type III in myocardial fibrosis [Elektronische Daten] [Ayako Uchinaka, Yoshinosuke Hamada, Seiji Mori, Shigeru Miyagawa, Atsuhiro Saito, Yoshiki Sawa, Nariaki Matsuura, Hirofumi Yamamoto, Naomasa Kawaguchi] Osteopontin (OPN) is involved in various physiological processes such as inflammatory and wound healing. However, little is known about the effects of OPN on these tissues. OPN is cleaved by thrombin, and cleavage of the N-terminal fragment exposes a SVVYGLR sequence on its C-terminus. In this study, we examined the effects of the thrombin-cleaved OPN fragments on fibroblasts and myocardial fibrosis, particularly the role of the SVVYGLR sequence. The recombinant thrombin-cleaved OPN fragments (N-terminal fragment [N-OPN], C-terminal fragment [C-OPN], and the N-terminal fragment lacking the SVVYGLR sequence [ΔSV N-OPN]) were added to fibroblasts, and the cellular motility, signal activity, and production of collagen were evaluated. A sustained-release gel containing an OPN fragment or SVVYGLR peptide was transplanted into a rat model of ischemic cardiomyopathy and the quantities and ratio of collagen type I (COL I) and type III (COL III) were estimated. N-OPN significantly promoted fibroblast migration. Smad signal activity, expression of smooth muscle actin (SMA), and the production of COL III were enhanced by N-OPN and SVVYGLR peptide. Conversely, ΔSV N-OPN and C-OPN had no effect. In vivo, the expression level of N-OPN was associated with COL III distribution, and the COL III/COL I ratio was significantly increased by the sustained-release gel containing N-OPN or SVVYGLR peptide. The cardiac function was also significantly improved by the N-OPN- or SVVYGLR peptide-released gel treatment. The N-terminal fragment of thrombin-cleaved OPN-induced Smad signal activation, SMA expression, and COL III production, and its SVVYGLR sequence influences this function. Springer Science+Business Media New York, 2015 Osteopontin nationallicence SVVYGLR peptide nationallicence Collagen type III nationallicence Fibrosis nationallicence Uchinaka Ayako Division of Health Sciences, Department of Cardiovascular Pathology, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, 565-0871, Suita, Osaka, Japan aut Hamada Yoshinosuke Division of Health Sciences, Department of Cardiovascular Pathology, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, 565-0871, Suita, Osaka, Japan aut Mori Seiji Division of Health Sciences, Department of Molecular Pathology, Osaka University Graduate School of Medicine, Suita, Japan aut Miyagawa Shigeru Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Japan aut Saito Atsuhiro Medical Center of Translational Research, Osaka University Graduate School of Medicine, Suita, Japan aut Sawa Yoshiki Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Japan aut Matsuura Nariaki Division of Health Sciences, Department of Molecular Pathology, Osaka University Graduate School of Medicine, Suita, Japan aut Yamamoto Hirofumi Division of Health Sciences, Department of Molecular Pathology, Osaka University Graduate School of Medicine, Suita, Japan aut Kawaguchi Naomasa Division of Health Sciences, Department of Cardiovascular Pathology, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, 565-0871, Suita, Osaka, Japan aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 408/1-2(2015-10-01), 191-203 0300-8177 408:1-2<191 2015 408 11010 https://doi.org/10.1007/s11010-015-2495-y text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2495-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Uchinaka Ayako Division of Health Sciences, Department of Cardiovascular Pathology, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, 565-0871, Suita, Osaka, Japan aut NATIONALLICENCE 700 1- Hamada Yoshinosuke Division of Health Sciences, Department of Cardiovascular Pathology, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, 565-0871, Suita, Osaka, Japan aut NATIONALLICENCE 700 1- Mori Seiji Division of Health Sciences, Department of Molecular Pathology, Osaka University Graduate School of Medicine, Suita, Japan aut NATIONALLICENCE 700 1- Miyagawa Shigeru Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Japan aut NATIONALLICENCE 700 1- Saito Atsuhiro Medical Center of Translational Research, Osaka University Graduate School of Medicine, Suita, Japan aut NATIONALLICENCE 700 1- Sawa Yoshiki Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Japan aut NATIONALLICENCE 700 1- Matsuura Nariaki Division of Health Sciences, Department of Molecular Pathology, Osaka University Graduate School of Medicine, Suita, Japan aut NATIONALLICENCE 700 1- Yamamoto Hirofumi Division of Health Sciences, Department of Molecular Pathology, Osaka University Graduate School of Medicine, Suita, Japan aut NATIONALLICENCE 700 1- Kawaguchi Naomasa Division of Health Sciences, Department of Cardiovascular Pathology, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, 565-0871, Suita, Osaka, Japan aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 408/1-2(2015-10-01), 191-203 0300-8177 408:1-2<191 2015 408 11010