Reduced sulfation of muc5b is linked to xerostomia in patients with Sjögren syndrome

C Alliende; Y-J Kwon; M Brito; C Molina; S Aguilera; P Pérez; L Leyton; A F G Quest; U Mandel; E Veerman; M Espinosa; H Clausen; C Leyton; R Romo; M-J González

doi:10.1136/ard.2007.078246

Reduced sulfation of muc5b is linked to xerostomia in patients with Sjögren syndrome

C Alliende, Y-J Kwon, M Brito, C Molina, S Aguilera, P Pérez, L Leyton, A F G Quest, U Mandel, E Veerman, M Espinosa, H Clausen, C Leyton, R Romo, M-J González

Department of Cellular and Molecular Medicine

41 Citations (Scopus)

Abstract

OBJECTIVES: MUC5B contains sulfated and sialylated oligosaccharides that sequester water required for moisturising the oral mucosa. Xerostomia, in patients with Sjögren syndrome, is generally associated with reduced quantities, rather than altered properties, of saliva. Here, we determined the amount of MUC5B (mRNA and protein) as well as sulfation levels in salivary glands of patients with normal or altered unstimulated salivary flow. Localisation of MUC5B and sulfated MUC5B, as well as total levels sulfated groups were determined and compared with acini basal lamina disorganisation. PATIENTS AND METHODS: In all, 18 patients with normal or altered unstimulated salivary flow and 16 controls were studied. MUC5B mRNA and protein were evaluated in salivary glands by semiquantitative RT-PCR and Western blot analysis. MUC5B sulfation was determined by Western blotting. MUC5B and sulfo-Lewis(a) antigen localisation were assessed by immunohistochemistry. The total amount of sulfated oligosaccharides was determined microdensitometrically. RESULTS: No significant differences were detected in MUC5B mRNA and protein levels between controls and patients, while sulfo-Lewis(a) antigen levels were lower in patients. The number of sulfo-Lewis(a) positive mucous acini was reduced in patients but no correlation was observed between lower levels of sulfation and unstimulated salivary flow. Microdensitometric data confirmed the presence of reduced sulfated oligosaccharides levels in mucous acini from patients with highly disorganised basal lamina. CONCLUSION: Disorganisation of the basal lamina observed in patients with Sjögren syndrome may lead to dedifferentiation of acinar mucous cells and, as a consequence, alter sulfation of MUC5B. These changes are suggested to represent a novel mechanism that may explain xerostomia in these patients.

Original language	English
Journal	Annals of the Rheumatic Diseases
Volume	67
Issue number	10
Pages (from-to)	1480-7
Number of pages	7
ISSN	0003-4967
DOIs	https://doi.org/10.1136/ard.2007.078246
Publication status	Published - 2008

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10.1136/ard.2007.078246

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Alliende, C., Kwon, Y-J., Brito, M., Molina, C., Aguilera, S., Pérez, P., Leyton, L., Quest, A. F. G., Mandel, U., Veerman, E., Espinosa, M., Clausen, H., Leyton, C., Romo, R., & González, M-J. (2008). Reduced sulfation of muc5b is linked to xerostomia in patients with Sjögren syndrome. Annals of the Rheumatic Diseases, 67(10), 1480-7. https://doi.org/10.1136/ard.2007.078246

Alliende, C, Kwon, Y-J, Brito, M, Molina, C, Aguilera, S, Pérez, P, Leyton, L, Quest, AFG, Mandel, U, Veerman, E, Espinosa, M, Clausen, H, Leyton, C, Romo, R & González, M-J 2008, 'Reduced sulfation of muc5b is linked to xerostomia in patients with Sjögren syndrome', Annals of the Rheumatic Diseases, vol. 67, no. 10, pp. 1480-7. https://doi.org/10.1136/ard.2007.078246

@article{7f502fb007ff11de8478000ea68e967b,

title = "Reduced sulfation of muc5b is linked to xerostomia in patients with Sj{\"o}gren syndrome",

abstract = "OBJECTIVES: MUC5B contains sulfated and sialylated oligosaccharides that sequester water required for moisturising the oral mucosa. Xerostomia, in patients with Sj{\"o}gren syndrome, is generally associated with reduced quantities, rather than altered properties, of saliva. Here, we determined the amount of MUC5B (mRNA and protein) as well as sulfation levels in salivary glands of patients with normal or altered unstimulated salivary flow. Localisation of MUC5B and sulfated MUC5B, as well as total levels sulfated groups were determined and compared with acini basal lamina disorganisation. PATIENTS AND METHODS: In all, 18 patients with normal or altered unstimulated salivary flow and 16 controls were studied. MUC5B mRNA and protein were evaluated in salivary glands by semiquantitative RT-PCR and Western blot analysis. MUC5B sulfation was determined by Western blotting. MUC5B and sulfo-Lewis(a) antigen localisation were assessed by immunohistochemistry. The total amount of sulfated oligosaccharides was determined microdensitometrically. RESULTS: No significant differences were detected in MUC5B mRNA and protein levels between controls and patients, while sulfo-Lewis(a) antigen levels were lower in patients. The number of sulfo-Lewis(a) positive mucous acini was reduced in patients but no correlation was observed between lower levels of sulfation and unstimulated salivary flow. Microdensitometric data confirmed the presence of reduced sulfated oligosaccharides levels in mucous acini from patients with highly disorganised basal lamina. CONCLUSION: Disorganisation of the basal lamina observed in patients with Sj{\"o}gren syndrome may lead to dedifferentiation of acinar mucous cells and, as a consequence, alter sulfation of MUC5B. These changes are suggested to represent a novel mechanism that may explain xerostomia in these patients.",

author = "C Alliende and Y-J Kwon and M Brito and C Molina and S Aguilera and P P{\'e}rez and L Leyton and Quest, {A F G} and U Mandel and E Veerman and M Espinosa and H Clausen and C Leyton and R Romo and M-J Gonz{\'a}lez",

note = "Keywords: Adult; Densitometry; Female; Gene Expression; Humans; Middle Aged; Mucin-5B; Mucins; Oligosaccharides; RNA, Messenger; Salivary Glands; Salivation; Sjogren's Syndrome; Sulfates; Xerostomia",

year = "2008",

doi = "10.1136/ard.2007.078246",

language = "English",

volume = "67",

pages = "1480--7",

journal = "Annals of the Rheumatic Diseases",

issn = "0003-4967",

publisher = "B M J Group",

number = "10",

}

TY - JOUR

T1 - Reduced sulfation of muc5b is linked to xerostomia in patients with Sjögren syndrome

AU - Alliende, C

AU - Kwon, Y-J

AU - Brito, M

AU - Molina, C

AU - Aguilera, S

AU - Pérez, P

AU - Leyton, L

AU - Quest, A F G

AU - Mandel, U

AU - Veerman, E

AU - Espinosa, M

AU - Clausen, H

AU - Leyton, C

AU - Romo, R

AU - González, M-J

N1 - Keywords: Adult; Densitometry; Female; Gene Expression; Humans; Middle Aged; Mucin-5B; Mucins; Oligosaccharides; RNA, Messenger; Salivary Glands; Salivation; Sjogren's Syndrome; Sulfates; Xerostomia

PY - 2008

Y1 - 2008

N2 - OBJECTIVES: MUC5B contains sulfated and sialylated oligosaccharides that sequester water required for moisturising the oral mucosa. Xerostomia, in patients with Sjögren syndrome, is generally associated with reduced quantities, rather than altered properties, of saliva. Here, we determined the amount of MUC5B (mRNA and protein) as well as sulfation levels in salivary glands of patients with normal or altered unstimulated salivary flow. Localisation of MUC5B and sulfated MUC5B, as well as total levels sulfated groups were determined and compared with acini basal lamina disorganisation. PATIENTS AND METHODS: In all, 18 patients with normal or altered unstimulated salivary flow and 16 controls were studied. MUC5B mRNA and protein were evaluated in salivary glands by semiquantitative RT-PCR and Western blot analysis. MUC5B sulfation was determined by Western blotting. MUC5B and sulfo-Lewis(a) antigen localisation were assessed by immunohistochemistry. The total amount of sulfated oligosaccharides was determined microdensitometrically. RESULTS: No significant differences were detected in MUC5B mRNA and protein levels between controls and patients, while sulfo-Lewis(a) antigen levels were lower in patients. The number of sulfo-Lewis(a) positive mucous acini was reduced in patients but no correlation was observed between lower levels of sulfation and unstimulated salivary flow. Microdensitometric data confirmed the presence of reduced sulfated oligosaccharides levels in mucous acini from patients with highly disorganised basal lamina. CONCLUSION: Disorganisation of the basal lamina observed in patients with Sjögren syndrome may lead to dedifferentiation of acinar mucous cells and, as a consequence, alter sulfation of MUC5B. These changes are suggested to represent a novel mechanism that may explain xerostomia in these patients.

AB - OBJECTIVES: MUC5B contains sulfated and sialylated oligosaccharides that sequester water required for moisturising the oral mucosa. Xerostomia, in patients with Sjögren syndrome, is generally associated with reduced quantities, rather than altered properties, of saliva. Here, we determined the amount of MUC5B (mRNA and protein) as well as sulfation levels in salivary glands of patients with normal or altered unstimulated salivary flow. Localisation of MUC5B and sulfated MUC5B, as well as total levels sulfated groups were determined and compared with acini basal lamina disorganisation. PATIENTS AND METHODS: In all, 18 patients with normal or altered unstimulated salivary flow and 16 controls were studied. MUC5B mRNA and protein were evaluated in salivary glands by semiquantitative RT-PCR and Western blot analysis. MUC5B sulfation was determined by Western blotting. MUC5B and sulfo-Lewis(a) antigen localisation were assessed by immunohistochemistry. The total amount of sulfated oligosaccharides was determined microdensitometrically. RESULTS: No significant differences were detected in MUC5B mRNA and protein levels between controls and patients, while sulfo-Lewis(a) antigen levels were lower in patients. The number of sulfo-Lewis(a) positive mucous acini was reduced in patients but no correlation was observed between lower levels of sulfation and unstimulated salivary flow. Microdensitometric data confirmed the presence of reduced sulfated oligosaccharides levels in mucous acini from patients with highly disorganised basal lamina. CONCLUSION: Disorganisation of the basal lamina observed in patients with Sjögren syndrome may lead to dedifferentiation of acinar mucous cells and, as a consequence, alter sulfation of MUC5B. These changes are suggested to represent a novel mechanism that may explain xerostomia in these patients.

U2 - 10.1136/ard.2007.078246

DO - 10.1136/ard.2007.078246

M3 - Journal article

C2 - 17998215

SN - 0003-4967

VL - 67

SP - 1480

EP - 1487

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 10

ER -

Reduced sulfation of muc5b is linked to xerostomia in patients with Sjögren syndrome

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