Global Loss of Core 1-Derived O-Glycans in Mice Leads to High Mortality Due to Acute Kidney Failure and Gastric Ulcers
Abstract
:1. Introduction
2. Results and Discussion
2.1. Ubiquitous Loss of Core 1-Derived O-Glycans Leads to High Mortality of Mice and Decrease in the Weight of Multiple Organs
2.2. iCAG-Cos Mice Exhibit Atrophy of the Thymus and Adipocytes and Acute Pancreatitis
2.3. iCAG-Cos Mice Show the Presence of Spontaneous Gastric Ulcers
2.4. iCAG-Cos Mice Show Renal Injury with Albuminuria
3. Materials and Methods
3.1. Animals
3.2. Helix Pomatia Agglutinin Analysis
3.3. Urine Analysis
3.4. Serological Analysis
3.5. Histological Analysis
3.6. Quantitative Analysis of Transcripts Using RT-qPCR
3.7. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Ju, T.; Brewer, K.; D’Souza, A.; Cummings, R.D.; Canfield, W.M. Cloning and expression of human core 1 beta1,3-galactosyltransferase. J. Biol. Chem. 2002, 277, 178–186. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ju, T.; Cummings, R.D. A unique molecular chaperone Cosmc required for activity of the mammalian core 1 beta 3-galactosyltransferase. Proc. Natl. Acad. Sci. USA 2002, 99, 16613–16618. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Alexander, W.S.; Viney, E.M.; Zhang, J.G.; Metcalf, D.; Kauppi, M.; Hyland, C.D.; Carpinelli, M.R.; Stevenson, W.; Croker, B.A.; Hilton, A.A.; et al. Thrombocytopenia and kidney disease in mice with a mutation in the C1galt1 gene. Proc. Natl. Acad. Sci. USA 2006, 103, 16442–16447. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, Y.; Jobe, S.M.; Ding, X.; Choo, H.; Archer, D.R.; Mi, R.; Ju, T.; Cummings, R.D. Platelet biogenesis and functions require correct protein O-glycosylation. Proc. Natl. Acad. Sci. USA 2012, 109, 16143–16148. [Google Scholar] [CrossRef] [Green Version]
- Kudo, T.; Sato, T.; Hagiwara, K.; Kozuma, Y.; Yamaguchi, T.; Ikehara, Y.; Hamada, M.; Matsumoto, K.; Ema, M.; Murata, S.; et al. C1galt1-deficient mice exhibit thrombocytopenia due to abnormal terminal differentiation of megakaryocytes. Blood 2013, 122, 1649–1657. [Google Scholar] [CrossRef] [Green Version]
- Wakui, H.; Fuseya, S.; Suzuki, R.; Shimbo, M.; Okada, R.; Hamada, M.; Kuno, A.; Hagiwara, K.; Sato, T.; Narimatsu, H.; et al. Incomplete clearance of apoptotic cells by core 1-derived O-glycan-deficient resident peritoneal macrophages. Biochem. Biophys. Res. Commun. 2018, 495, 2017–2023. [Google Scholar] [CrossRef]
- Song, K.; Fu, J.; Song, J.; Herzog, B.H.; Bergstrom, K.; Kondo, Y.; McDaniel, J.M.; McGee, S.; Silasi-Mansat, R.; Lupu, F.; et al. Loss of mucin-type O-glycans impairs the integrity of the glomerular filtration barrier in the mouse kidney. J. Biol. Chem. 2017, 292, 16491–16497. [Google Scholar] [CrossRef] [PubMed]
- Fuseya, S.; Suzuki, R.; Okada, R.; Hagiwara, K.; Sato, T.; Narimatsu, H.; Yokoi, H.; Kasahara, M.; Usui, T.; Morito, N.; et al. Mice lacking core 1-derived O-glycan in podocytes develop transient proteinuria, resulting in focal segmental glomerulosclerosis. Biochem. Biophys. Res. Commun. 2020, 523, 1007–1013. [Google Scholar] [CrossRef]
- Zeng, J.; Eljalby, M.; Aryal, R.P.; Lehoux, S.; Stavenhagen, K.; Kudelka, M.R.; Wang, Y.; Wang, J.; Ju, T.; von Andrian, U.H.; et al. Cosmc controls B cell homing. Nat. Commun. 2020, 11, 3990. [Google Scholar] [CrossRef]
- Lowenthal, M.S.; Davis, K.S.; Formolo, T.; Kilpatrick, L.E.; Phinney, K.W. Identification of Novel N-Glycosylation Sites at Noncanonical Protein Consensus Motifs. J. Proteome. Res. 2016, 15, 2087–2101. [Google Scholar] [CrossRef]
- Kuchroo, V.K.; Umetsu, D.T.; DeKruyff, R.H.; Freeman, G.J. The TIM gene family: Emerging roles in immunity and disease. Nat. Rev. Immunol. 2003, 3, 454–462. [Google Scholar] [CrossRef]
- Linden, S.K.; Sutton, P.; Karlsson, N.G.; Korolik, V.; McGuckin, M.A. Mucins in the mucosal barrier to infection. Mucosal. Immunol. 2008, 1, 183–197. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cutler, C.E.; Jones, M.B.; Cutler, A.A.; Mener, A.; Arthur, C.M.; Stowell, S.R.; Cummings, R.D. Cosmc is required for T cell persistence in the periphery. Glycobiology 2019, 29, 776–788. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, Y.; Fu, J.; Ling, Y.; Yago, T.; McDaniel, J.M.; Song, J.; Bai, X.; Kondo, Y.; Qin, Y.; Hoover, C.; et al. Sialylation on O-glycans protects platelets from clearance by liver Kupffer cells. Proc. Natl. Acad. Sci. USA 2017, 114, 8360–8365. [Google Scholar] [CrossRef] [Green Version]
- Betjes, M.G. Uremia-Associated Ageing of the Thymus and Adaptive Immune Responses. Toxins 2020, 12, 224. [Google Scholar] [CrossRef] [Green Version]
- Ueno, K.; Ajiki, T.; Watanabe, H.; Abo, T.; Takeyama, Y.; Onoyama, H.; Kuroda, Y. Changes in extrathymic T cells in the liver and intestinal intraepithelium in mice with obstructive jaundice. World J. Surg. 2004, 28, 277–282. [Google Scholar] [PubMed] [Green Version]
- Tang, H.N.; Tang, C.Y.; Man, X.F.; Tan, S.W.; Guo, Y.; Tang, J.; Zhou, C.L.; Zhou, H.D. Plasticity of adipose tissue in response to fasting and refeeding in male mice. Nutr. Metab. 2017, 14, 3. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chau, Y.Y.; Brownstein, D.; Mjoseng, H.; Lee, W.C.; Buza-Vidas, N.; Nerlov, C.; Jacobsen, S.E.; Perry, P.; Berry, R.; Thornburn, A.; et al. Acute multiple organ failure in adult mice deleted for the developmental regulator Wt1. PLoS Genet. 2011, 7, e1002404. [Google Scholar] [CrossRef] [Green Version]
- Wolters-Eisfeld, G.; Mercanoglu, B.; Hofmann, B.T.; Wolpers, T.; Schnabel, C.; Harder, S.; Steffen, P.; Bachmann, K.; Steglich, B.; Schrader, J.; et al. Loss of complex O-glycosylation impairs exocrine pancreatic function and induces MODY8-like diabetes in mice. Exp. Mol. Med. 2018, 50, 1–13. [Google Scholar] [CrossRef] [Green Version]
- Mentula, P.; Kylanpaa, M.L.; Kemppainen, E.; Puolakkainen, P. Obesity correlates with early hyperglycemia in patients with acute pancreatitis who developed organ failure. Pancreas 2008, 36, e21–e25. [Google Scholar] [CrossRef]
- Liu, F.; Fu, J.; Bergstrom, K.; Shan, X.; McDaniel, J.M.; McGee, S.; Bai, X.; Chen, W.; Xia, L. Core 1-derived mucin-type O-glycosylation protects against spontaneous gastritis and gastric cancer. J. Exp. Med. 2020, 217, e20182325. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fu, J.; Wei, B.; Wen, T.; Johansson, M.E.; Liu, X.; Bradford, E.; Thomsson, K.A.; McGee, S.; Mansour, L.; Tong, M.; et al. Loss of intestinal core 1-derived O-glycans causes spontaneous colitis in mice. J. Clin. Investig. 2011, 121, 1657–1666. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Iwai, T.; Inaba, N.; Naundorf, A.; Zhang, Y.; Gotoh, M.; Iwasaki, H.; Kudo, T.; Togayachi, A.; Ishizuka, Y.; Nakanishi, H.; et al. Molecular cloning and characterization of a novel UDP-GlcNAc:GalNAc-peptide beta1,3-N-acetylglucosaminyltransferase (beta 3Gn-T6), an enzyme synthesizing the core 3 structure of O-glycans. J. Biol. Chem. 2002, 277, 12802–12809. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- An, G.; Wei, B.; Xia, B.; McDaniel, J.M.; Ju, T.; Cummings, R.D.; Braun, J.; Xia, L. Increased susceptibility to colitis and colorectal tumors in mice lacking core 3-derived O-glycans. J. Exp. Med. 2007, 204, 1417–1429. [Google Scholar] [CrossRef]
- Gao, N.; Bergstrom, K.; Fu, J.; Xie, B.; Chen, W.; Xia, L. Loss of intestinal O-glycans promotes spontaneous duodenal tumors. Am. J. Physiol. Gastrointest. Liver Physiol. 2016, 311, G74–G83. [Google Scholar] [CrossRef] [Green Version]
- Bergstrom, K.; Fu, J.; Johansson, M.E.; Liu, X.; Gao, N.; Wu, Q.; Song, J.; McDaniel, J.M.; McGee, S.; Chen, W.; et al. Core 1- and 3-derived O-glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice. Mucosal. Immunol. 2017, 10, 91–103. [Google Scholar] [CrossRef] [Green Version]
- Usui, T.; Morito, N.; Shawki, H.H.; Sato, Y.; Tsukaguchi, H.; Hamada, M.; Jeon, H.; Yadav, M.K.; Kuno, A.; Tsunakawa, Y.; et al. Transcription factor MafB in podocytes protects against the development of focal segmental glomerulosclerosis. Kidney Int. 2020, 98, 391–403. [Google Scholar] [CrossRef]
- Vaidya, V.S.; Ozer, J.S.; Dieterle, F.; Collings, F.B.; Ramirez, V.; Troth, S.; Muniappa, N.; Thudium, D.; Gerhold, D.; Holder, D.J.; et al. Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nat. Biotechnol. 2010, 28, 478–485. [Google Scholar] [CrossRef] [Green Version]
- Moresco, R.N.; Bochi, G.V.; Stein, C.S.; De Carvalho, J.A.M.; Cembranel, B.M.; Bollick, Y.S. Urinary kidney injury molecule-1 in renal disease. Clin. Chim. Acta 2018, 487, 15–21. [Google Scholar] [CrossRef]
- Yang, L.; Brooks, C.R.; Xiao, S.; Sabbisetti, V.; Yeung, M.Y.; Hsiao, L.L.; Ichimura, T.; Kuchroo, V.; Bonventre, J.V. KIM-1-mediated phagocytosis reduces acute injury to the kidney. J. Clin. Investig. 2015, 125, 1620–1636. [Google Scholar] [CrossRef]
- Chan, D.T.; Dogra, G.K.; Irish, A.B.; Ooi, E.M.; Barrett, P.H.; Chan, D.C.; Watts, G.F. Chronic kidney disease delays VLDL-apoB-100 particle catabolism: Potential role of apolipoprotein C-III. J. Lipid Res. 2009, 50, 2524–2531. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, S.; Mao, Y.; Narimatsu, Y.; Ye, Z.; Tian, W.; Goth, C.K.; Lira-Navarrete, E.; Pedersen, N.B.; Benito-Vicente, A.; Martin, C.; et al. Site-specific O-glycosylation of members of the low-density lipoprotein receptor superfamily enhances ligand interactions. J. Biol. Chem. 2018, 293, 7408–7422. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hayashi, S.; McMahon, A.P. Efficient recombination in diverse tissues by a tamoxifen-inducible form of Cre: A tool for temporally regulated gene activation/inactivation in the mouse. Dev. Biol. 2002, 244, 305–318. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Inspection Item | Control (n = 9) | iCAG-Cos (n = 11) | p-Value |
---|---|---|---|
Glucose (mmol/L) | 11.88 ± 0.51 | 7.34 ± 0.55 | 0.00 |
Triglyceride (mmol/L) | 0.71 ± 0.11 | 2.04 ± 0.45 | 0.02 |
Total cholesterol (mmol/L) | 1.06 ± 0.04 | 4.22 ± 0.58 | 0.00 |
HDL 1 (mg/dL) | 0.81 ± 0.08 | 2.64 ± 0.31 | 0.01 |
Total protein (g/L) | 35.01 ± 1.55 | 28.80 ± 0.16 | 0.02 |
AST 2 (U/L) | 28.67 ± 1.49 | 42.55 ± 6.19 | 0.05 |
ALT 3 (U/L) | 24.33 ± 2.60 | 33.77 ± 1.41 | 0.01 |
Total bilirubin (µmol/L) | 5.12 ± 0.32 | 4.97 ± 0.69 | 0.85 |
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Suzuki, R.; Nakamura, Y.; Koiwai, R.; Fuseya, S.; Murakami, Y.; Hagiwara, K.; Sato, T.; Takahashi, S.; Kudo, T. Global Loss of Core 1-Derived O-Glycans in Mice Leads to High Mortality Due to Acute Kidney Failure and Gastric Ulcers. Int. J. Mol. Sci. 2022, 23, 1273. https://doi.org/10.3390/ijms23031273
Suzuki R, Nakamura Y, Koiwai R, Fuseya S, Murakami Y, Hagiwara K, Sato T, Takahashi S, Kudo T. Global Loss of Core 1-Derived O-Glycans in Mice Leads to High Mortality Due to Acute Kidney Failure and Gastric Ulcers. International Journal of Molecular Sciences. 2022; 23(3):1273. https://doi.org/10.3390/ijms23031273
Chicago/Turabian StyleSuzuki, Riku, Yuki Nakamura, Rikako Koiwai, Sayaka Fuseya, Yuka Murakami, Kozue Hagiwara, Takashi Sato, Satoru Takahashi, and Takashi Kudo. 2022. "Global Loss of Core 1-Derived O-Glycans in Mice Leads to High Mortality Due to Acute Kidney Failure and Gastric Ulcers" International Journal of Molecular Sciences 23, no. 3: 1273. https://doi.org/10.3390/ijms23031273