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Cited by 731Proteoglycans and glycosaminoglycans researchConnective tissue disorders researchCorneal surgery and disorders

Lumican regulates collagen fibril assembly: skin fragility and corneal opacity in the absence of lumican

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Chakravarti, Shukti, Magnuson, Terry, Lass, Jonathan H., Jepsen, Karl J., LaMantia, Christian, Carroll, Heidi·1998·The Journal of Cell Biology
DOI 10.1083/jcb.141.5.1277PMC PMC2137175
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Abstract

Lumican, a prototypic leucine-rich proteoglycan with keratan sulfate side chains, is a major component of the cornea, dermal, and muscle connective tissues. Mice homozygous for a null mutation in lumican display skin laxity and fragility resembling certain types of Ehlers-Danlos syndrome. In addition, the mutant mice develop bilateral corneal opacification. The underlying connective tissue defect in the homozygous mutants is deregulated growth of collagen fibrils with a significant proportion of abnormally thick collagen fibrils in the skin and cornea as indicated by transmission electron microscopy. A highly organized and regularly spaced collagen fibril matrix typical of the normal cornea is also missing in these mutant mice. This study establishes a crucial role for lumican in the regulation of collagen assembly into fibrils in various connective tissues. Most importantly, these results provide a definitive link between a necessity for lumican in the development of a highly organized collagenous matrix and corneal transparency.

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  • Corneal structural defects of this type are associated with genetic mutations involving proteoglycans, which seem to affect the repulsive forces between adjacent fibrils and allow them to fuse.

    “Corneal structural defects of this type are associated, for example, with genetic mutations involving proteoglycans (Chakravarti et al., 1998) which, ultimately, seem to have an effect on the repulsive forces between adjacent fibrils and allow them to fuse together.”

    From Corneal structure and transparency (2015) · cites this paper as Chakravarti et al., 1998

    The Discussion reports corneal opacity in mice with a null mutation of the lumican gene, and its collagen-fibril section describes frequent lateral fusion of fibrils. The paper proposes that proteoglycan core proteins discourage lateral fusion, but it does not identify a change in repulsive forces between adjacent fibrils as the mechanism. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Studies of mutant mice unable to produce necessary amounts of lumican, decorin and biglycan in the cornea confirmed the effect of proteoglycan cores on fibril size.

    “These findings were confirmed in studies of mutant mice unable to produce the necessary amount of lumican, decorin and biglycan in the cornea (Chakravarti et al., 1998, Chakravarti et al., 2006, Zhang et al., 2008).”

    From Corneal structure and transparency (2015) · cites this paper as Chakravarti et al., 1998

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Cites

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Research works printed but not linked: 43

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Authors
Chakravarti, S., Magnuson, T., Lass, J. H., Jepsen, K. J., LaMantia, C., & Carroll, H.
Affiliations
University Hospitals of Cleveland (US)
Corresponding author
Chakravarti, Shukti
ORCID
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
1998-06-01
Volume
141
Issue
5
Pages
1277-1286
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.141.5.1277
PMC
PMC2137175
OpenAlex
W2159058635
Cited by
731
References
1
Citations by year
2026: 13 · 2025: 20 · 2024: 15 · 2023: 25 · 2022: 18 · 2021: 36 · 2020: 36 · 2019: 21 · 2018: 18 · 2017: 27 · 2016: 29 · 2015: 32 · 2014: 24 · 2013: 29 · 2012: 13
FWCI
8.68
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • National Eye Institute (EY11654, EY-11373, R01EY011654, R56EY011654, P30EY011373)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD26722, R01HD026722)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Corneal surgery and disorders
Keywords
lumican, collagen fibril assembly, keratan sulfate proteoglycan, skin fragility, skin laxity, corneal opacity, corneal transparency, Ehlers-Danlos syndrome, connective tissue, null mice
MeSH terms
Lumican, Animals, Collagen, Corneal Opacity, Keratan Sulfate, Chondroitin Sulfate Proteoglycans, Skin Diseases, Metabolic, Tensile Strength, Gene Expression, In Situ Hybridization, Gene Targeting, Mice

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