Dataset Information

Proteomic analysis of neonatal rats distal colon mucus

ABSTRACT: Compositional analysis of the neonatal rats distal colon mucus proteome by label-free mass spectrometry indicated significant variability in mucus protein composition at different ages.

INSTRUMENT(S):

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Mucus, Colon, Colonic Mucosa

SUBMITTER: Liisa Arike

LAB HEAD: Liisa Arike

PROVIDER: PXD052791 | Pride | 2025-04-01

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	160728_QEx_LA_MS573_40.raw	Raw
	160728_QEx_LA_MS573_41.raw	Raw
	160728_QEx_LA_MS573_42.raw	Raw
	160728_QEx_LA_MS573_43.raw	Raw
	160728_QEx_LA_MS573_44.raw	Raw

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Publications

Neonatal microbiota colonization drives maturation of primary and secondary goblet cell mediated protection in the pre-weaning colon.

Johansson Åsa Å Subramani Mahadevan Venkita MV Yilmaz Bahtiyar B Nyström Elisabeth E Layunta Elena E Arike Liisa L Sommer Felix F Rosenstiel Philip P Vereecke Lars L Holm Louise Mannerås LM Wullaert Andy A Pelaseyed Thaher T Johansson Malin E V MEV Birchenough George M H GMH

bioRxiv : the preprint server for biology 20240705

In the distal colon, mucus secreting goblet cells primarily confer protection from luminal microorganisms via generation of a sterile inner mucus layer barrier structure. Bacteria-sensing sentinel goblet cells provide a secondary defensive mechanism that orchestrates mucus secretion in response to microbes that breach the mucus barrier. Previous reports have identified mucus barrier deficiencies in adult germ-free mice, thus implicating a fundamental role for the microbiota in programming mucus ...[more]

PMID: 39005291

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Project description:In this study we compared the intestinal mucus phenotype of Clca1-deficient (Clca1-/-) mice and wild-type (WT) controls. The human CLCA1 (chloride channel regulator, calcium-activated) and its murine ortholog mouse CLCA1 (formerly known as CLCA3) are secreted proteins which have been linked to human respiratory diseases such as asthma, cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) as well as to the corresponding murine models of these diseases. Common, disease severity-related features are goblet cell hyperplasia, mucus overproduction and disturbed clearance. Neutralization of mouse CLCA1 ameliorates the symptoms in the asthmatic mouse model and restoration of the decreased mouse CLCA1 protein level in a CF mouse model ameliorates the intestinal CF lesions, pointing toward these proteins being potential therapeutic targets. The expression CLCA1 can be induced in airways but this protein is normally expressed and secreted by goblet cells of the intestinal tract in both human and mouse together with the intestinal MUC2 mucin. This makes CLCA1 a major constituent of the extracellular intestinal mucus in which the MUC2 mucin is the main structural component. To study the possible further effects of murine CLCA1 deficiency on Muc2 and on other important components of the mucus, such as Agr2, Fcgbp, Klk and Zg16, a shotgun label-free proteomics study was performed which compared their relative abundance in the mucus layer, showing a tight and significant correlation between WT and Clca1-/- mucus proteins (Pearson r = 0.931, r2 = 0.868, p < 0.0001, based on 809 valid pairs). No significant differences in known mucus protein expression were observed. However, the abundance of CLCA1 in the mucus together with the domain structure suggests a structural role and other methods to reveal the function of these domains might shed light on the overall function in mucus. Because of its abundance in the mucus and the well preserved structure thought a long evolution together with mucus we still speculate that CLCA1 was developed to protect the expressing organism, although the threat is elusive.