Complementary Role of GlcNAc6ST2 and GlcNAc6ST3 in Synthesis of CL40-Reactive Sialylated and Sulfated Glycans in the Mouse Pleural Mesothelium

Takeda-Uchimura, Yoshiko; Ikezaki, Midori; Akama, Tomoya O.; Nishioka, Kaho; Ihara, Yoshito; Allain, Fabrice; Nishitsuji, Kazuchika; Uchimura, Kenji

doi:10.3390/molecules27144543

Cited by 2 publications

(12 citation statements)

References 65 publications

(98 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unexpectedly, mice deficient in GlcNAc6ST2 showed negligible levels of pleural R-10G signals ( Figure 3 A,B). As seen in the previous report [ 3 ], the mesothelin-positive mesothelium was thickened in GlcNAc6ST2 KO and GlcNAc6ST3 KO mice ( Figure 3 A). R-10G signals in these KO mice were not colocalized with laminins ( Supplementary Materials Figure S2 ).…”

Section: Resultssupporting

confidence: 87%

“…We previously showed that the 6-sulfo sLe X present in the high endothelial venule (HEV) cells of peripheral lymph nodes is complementarily synthesized by GlcNAc6ST1 and GlcNAc6ST2 [ 15 , 16 ]. Recently, we reported that GlcNAc6ST2 and GlcNAc6ST3 are complementary to the synthesis of sialyl 6-sulfo LacNAc recognized by CL40 in the mouse pleura [ 3 ]. We wished to determine which GlcNAc6ST is responsible for the synthesis of R10G-reactive glycans in the mouse pleural mesothelium.…”

Section: Resultsmentioning

confidence: 99%

“…Ks 36) were obtained from Seikagaku Corporation (Tokyo, Japan). The enzyme pretreatments were optimized previously [ 3 , 37 ].…”

Section: Methodsmentioning

confidence: 99%

“…It is important to determine which GlcNAc6STs are involved in the synthesis of which sulfated glycans in a tissue-specific and cell-specific manner. Recently, we reported that sialyl 6-sulfo N -acetyllactosamine (sialyl 6-sulfo LacNAc, Neu5Acα2-3Galβ1-4(6S)GlcNAc), a sialylated GlcNAc-6-sulfated glycan recognized by the CL40 antibody [ 2 ], is present in the mesothelin-positive mesothelium of pulmonary pleura under physiological conditions [ 3 ]. We also reported that the synthesis of CL40-positive glycans in the mouse lung mesothelium requires GlcNAc6ST2 (encoded by Chst4 ) and GlcNAc6ST3 (encoded by Chst5 ) but not GlcNAc6ST1 (encoded by Chst2 ) or GlcNAc6ST4 (encoded by Chst7 ) [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we reported that sialyl 6-sulfo N -acetyllactosamine (sialyl 6-sulfo LacNAc, Neu5Acα2-3Galβ1-4(6S)GlcNAc), a sialylated GlcNAc-6-sulfated glycan recognized by the CL40 antibody [ 2 ], is present in the mesothelin-positive mesothelium of pulmonary pleura under physiological conditions [ 3 ]. We also reported that the synthesis of CL40-positive glycans in the mouse lung mesothelium requires GlcNAc6ST2 (encoded by Chst4 ) and GlcNAc6ST3 (encoded by Chst5 ) but not GlcNAc6ST1 (encoded by Chst2 ) or GlcNAc6ST4 (encoded by Chst7 ) [ 3 ]. GlcNAc6ST2 and GlcNAc6ST3 are complementary to the synthesis of CL40-reactive sialylated sulfated glycans in the mouse pleural mesothelium.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

GlcNAc6ST2/CHST4 Is Essential for the Synthesis of R-10G-Reactive Keratan Sulfate/Sulfated N-Acetyllactosamine Oligosaccharides in Mouse Pleural Mesothelium

Takeda-Uchimura,

Ikezaki,

Akama

et al. 2024

Molecules

Self Cite

View full text Add to dashboard Cite

We recently showed that 6-sulfo sialyl N-acetyllactosamine (LacNAc) in O-linked glycans recognized by the CL40 antibody is abundant in the pleural mesothelium under physiological conditions and that these glycans undergo complementary synthesis by GlcNAc6ST2 (encoded by Chst4) and GlcNAc6ST3 (encoded by Chst5) in mice. GlcNAc6ST3 is essential for the synthesis of R-10G-positive keratan sulfate (KS) in the brain. The predicted minimum epitope of the R-10G antibody is a dimeric asialo 6-sulfo LacNAc. Whether R-10G-reactive KS/sulfated LacNAc oligosaccharides are also present in the pleural mesothelium was unknown. The question of which GlcNAc6STs are responsible for R-10G-reactive glycans was an additional issue to be clarified. Here, we show that R-10G-reactive glycans are as abundant in the pulmonary pleura as CL40-reactive glycans and that GlcNAc6ST3 is only partially involved in the synthesis of these pleural R-10G glycans, unlike in the adult brain. Unexpectedly, GlcNAc6ST2 is essential for the synthesis of R-10G-positive KS/sulfated LacNAc oligosaccharides in the lung pleura. The type of GlcNAc6ST and the magnitude of its contribution to KS glycan synthesis varied among tissues in vivo. We show that GlcNAc6ST2 is required and sufficient for R-10G-reactive KS synthesis in the lung pleura. Interestingly, R-10G immunoreactivity in KSGal6ST (encoded by Chst1) and C6ST1 (encoded by Chst3) double-deficient mouse lungs was markedly increased. MUC16, a mucin molecule, was shown to be a candidate carrier protein for pleural R-10G-reactive glycans. These results suggest that R-10G-reactive KS/sulfated LacNAc oligosaccharides may play a role in mesothelial cell proliferation and differentiation. Further elucidation of the functions of sulfated glycans synthesized by GlcNAc6ST2 and GlcNAc6ST3, such as R-10G and CL40 glycans, in pathological conditions may lead to a better understanding of the underlying mechanisms of the physiopathology of the lung mesothelium.

show abstract

Section: Resultssupporting

confidence: 87%

Section: Resultsmentioning

confidence: 99%

“…Ks 36) were obtained from Seikagaku Corporation (Tokyo, Japan). The enzyme pretreatments were optimized previously [ 3 , 37 ].…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

GlcNAc6ST2/CHST4 Is Essential for the Synthesis of R-10G-Reactive Keratan Sulfate/Sulfated N-Acetyllactosamine Oligosaccharides in Mouse Pleural Mesothelium

Takeda-Uchimura,

Ikezaki,

Akama

et al. 2024

Molecules

Self Cite

View full text Add to dashboard Cite

show abstract

GlcNAc6ST2/Chst4 Is Essential for the Synthesis of R-10G-Reactive Keratan Sulfate/Sulfated N-acetyllactosamine Oligosaccharides in Mouse Pleural Mesothelium

Takeda-Uchimura,

Ikezaki,

Akama

et al. 2023

Preprint

View full text Add to dashboard Cite

We have recently shown that 6-sulfo sialyl N-acetyllactosamine (LacNAc) in O-linked glycan recognized by the CL40 antibody is abundant in the pleural mesothelium under physiological conditions, and that these glycans are complementary synthesized by GlcNAc6ST2 (encoded by Chst4) and GlcNAc6ST3 (encoded by Chst5) in mice. GlcNAc6ST3 is essential for the synthesis of R-10G-positive keratan sulfate (KS) in the brain. The predicted minimum epitope of the R-10G antibody is a dimeric asialo 6-sulfo LacNAc. Whether the R-10G-reactive KS/sulfated LacNAc oligosaccharides are also present in the pleural mesothelium was unknown. If any, the question of which GlcNAc6ST is the responsible enzyme was another issue to be examined as well. Here, we showed that R-10G-reactive glycans are as abundant in the pulmonary pleura as are CL40-reactive glycans, and that GlcNAc6ST3 is only partially involved in the synthesis of these pleural R-10G glycans, unlike in the adult brain. Unexpectedly, GlcNAc6ST2 is essential for the synthesis of R-10G-positive KS/sulfated LacNAc oligosaccharides in the lung pleura. The type of GlcNAc6ST involved in KS glycan biosynthesis and the magnitude of its contribution to the KS synthesis were found to differ among tissues in vivo. We show that GlcNAc6ST2 is required and sufficient for R-10G-reactive KS synthesis in the lung pleura. Interestingly, R-10G immunoreactivity in KSGal6ST (encoded by Chst1) and C6st1 (encoded by Chst3) double-deficient mouse lungs was markedly increased. Muc16, a mucin molecule, was shown to be a candidate carrier protein for the pleural R-10G-reactive glycans. These results suggested that R-10G-positive KS/sulfated LacNAc oligosaccharides may play a role in mesothelial cell proliferation and differentiation. Further elucidation of the functions of sulfated glycans synthesized by GlcNAc6ST2 and GlcNAc6ST3, such as R-10G and CL40 glycans, in pathological conditions may lead to a better understanding of the underlying mechanisms of the physiopathology of lung mesothelium.

show abstract

Complementary Role of GlcNAc6ST2 and GlcNAc6ST3 in Synthesis of CL40-Reactive Sialylated and Sulfated Glycans in the Mouse Pleural Mesothelium

Cited by 2 publications

References 65 publications

GlcNAc6ST2/CHST4 Is Essential for the Synthesis of R-10G-Reactive Keratan Sulfate/Sulfated N-Acetyllactosamine Oligosaccharides in Mouse Pleural Mesothelium

GlcNAc6ST2/CHST4 Is Essential for the Synthesis of R-10G-Reactive Keratan Sulfate/Sulfated N-Acetyllactosamine Oligosaccharides in Mouse Pleural Mesothelium

GlcNAc6ST2/Chst4 Is Essential for the Synthesis of R-10G-Reactive Keratan Sulfate/Sulfated N-acetyllactosamine Oligosaccharides in Mouse Pleural Mesothelium

Contact Info

Product

Resources

About