Enzymatic synthesis of hyaluronan hybrid urinary trypsin inhibitor

Kakizaki, Ikuko; Takahashi, Ryoki; Yanagisawa, Miho; Yoshida, Futaba; Takagaki, Keiichi

doi:10.1016/j.carres.2015.05.009

Cited by 6 publications

(7 citation statements)

References 40 publications

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“…HA hybrid-UTIs and Ch4S hybrid-UTIs were broadly distributed up to 50 kDa (Figure 2A, lanes 7, 8, 11, and 12). 20) The success of transglycosylation was confirmed by Alcian blue staining ( Figure 2B, lanes 5-12). Figure 3 shows the effect of UTIs on IL-8 release in the culture supernatant of UCFs after LPS stimulation.…”

Section: Resultsmentioning

confidence: 81%

“…18,19) Small populations of Ν-terminal truncated UTIs without GAG chains, which are low molecular weight UTI forms, were detected at approximately 17 kDa. 20,29) After the low-sulfated Ch4S chains of native UTIs were hydrolyzed (i.e., linkage-UTIs), two bands were detected at approximately 21.5 kDa and 17 kDa (Figure 2A, lanes 3 and 4). 20) HA-linkage-UTIs and Ch4S-linkage-UTIs were similar to linkage-UTIs, but they were more broadly distributed (Figure 2A, lanes 5, 6, 9, and 10).…”

Section: Resultsmentioning

confidence: 99%

“…20,29) After the low-sulfated Ch4S chains of native UTIs were hydrolyzed (i.e., linkage-UTIs), two bands were detected at approximately 21.5 kDa and 17 kDa (Figure 2A, lanes 3 and 4). 20) HA-linkage-UTIs and Ch4S-linkage-UTIs were similar to linkage-UTIs, but they were more broadly distributed (Figure 2A, lanes 5, 6, 9, and 10). HA hybrid-UTIs and Ch4S hybrid-UTIs were broadly distributed up to 50 kDa (Figure 2A, lanes 7, 8, 11, and 12).…”

Section: Resultsmentioning

confidence: 99%

“…We previously remodeled the chondroitin sulfate chain moiety of UTI, with the core protein intact, by glycotechnology using testicular hyaluronidase. 20) In this study, we aimed to clarify the role of the GAG chain in UTI's function. If GAG chain remodeling can impart a new function to UTI, our findings may help in the development of more effective therapeutic drugs for preterm birth.…”

Section: Introductionmentioning

confidence: 99%

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Development of new therapeutic agents for preterm birth by glycosaminoglycan chain remodeling of urinary trypsin inhibitor

Tanaka

Kakizaki

Kodama

et al. 2019

Hypertens Res Pregnancy

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This study aimed to examine the effects of the glycosaminoglycan (GAG) chain in urinary trypsin inhibitor (UTI) on uterine cervical fibroblasts (UCFs) and to apply the findings to the development of more effective therapeutic drugs for the management of preterm birth. Methods: We prepared GAG chain-remodeled UTIs by hydrolysis and /or transglycosylation by testicular hyaluronidase. These UTIs were added to UCFs obtained from gynecology operations, and the effects of UTIs on the release of IL-8, IL-6, MMP-8, and MMP-9 were examined. Results: UTIs that were not hydrolyzed tended to reduce IL-8 release more strongly than GAG chain-hydrolyzed UTIs. IL-6 was not affected by GAG chain hydrolysis of UTIs. GAG chain-hydrolyzed UTIs tended to reduce MMP-8 and MMP-9 release more strongly than non-hydrolyzed UTIs. Conclusions: Our findings suggest that the GAG chain of UTI might reduce hyaluronan during cervical ripening by reducing IL-8 release and has opposite effects on reducing MMP-8 and MMP-9 release related to collagen degradation. This insight may be helpful in the development of more effective therapeutic drugs for the management of preterm birth.

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Section: Resultsmentioning

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Development of new therapeutic agents for preterm birth by glycosaminoglycan chain remodeling of urinary trypsin inhibitor

Tanaka

Kakizaki

Kodama

et al. 2019

Hypertens Res Pregnancy

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“…Recently, we remodeled the GAG chain of UTI from low sulfated Ch4S to hyaluronan (HA), with no changes to the core protein to create the HA hybrid UTI (HA-UTI) as a tool for investigating native GAG chain functions as well as the possible superiority of HA-UTIs over native UTI. 13) 14) In the present study, we investigated the effect of the GAG chain on the activities of trypsin, chymotrypsin, plasmin, and pancreatic elastase. It was demonstrated that UTI having a native GAG chain showed stronger inhibitory activity on these proteases compared with HA-UTI or with UTI with only a linkage region as sugar chain moiety.…”

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confidence: 99%

A Chondroitin Sulfate Chain of Urinary Trypsin Inhibitor Enhances Protease Inhibitory Activity of the Core Protein

et al. 2020

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Human urinary trypsin inhibitor (UTI) is a proteoglycan composed of one core protein covalently linked to one glycosaminoglycan, which is a low sulfated chondroitin 4-sulfate. It is used as an anti-inflammatory medicine based on the protease inhibitory activity of the core protein. However, functions of the chondroitin sulfate have not been clarified. Recently, we succeeded in remodeling the UTI chondroitin sulfate to hyaluronan to create hyaluronan hybrid UTI, without changing the core protein. Here, we investigated the effect of the remodeled chondroitin sulfate on the activities of serine proteases. Native UTI showed stronger protease inhibitory activity than hyaluronan hybrid UTI or hydrolyzed glycosaminoglycan UTI. Chondroitin 4-sulfate chains with a small peptide derived from the native UTI did not show any protease inhibitory activity. These results suggest that the chondroitin sulfate chain linked covalently to core protein enhances protease inhibitor activity of UTI although the chondroitin sulfate chain itself does not.

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Essential hyaluronan structure for binding with hyaluronan-binding protein (HABP) determined by glycotechnological approach

Suto

Kakizaki

Tatara

et al. 2021

Carbohydrate Polymers

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Enzymatic synthesis of hyaluronan hybrid urinary trypsin inhibitor

Cited by 6 publications

References 40 publications

Development of new therapeutic agents for preterm birth by glycosaminoglycan chain remodeling of urinary trypsin inhibitor

Development of new therapeutic agents for preterm birth by glycosaminoglycan chain remodeling of urinary trypsin inhibitor

A Chondroitin Sulfate Chain of Urinary Trypsin Inhibitor Enhances Protease Inhibitory Activity of the Core Protein

Essential hyaluronan structure for binding with hyaluronan-binding protein (HABP) determined by glycotechnological approach

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