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Tissue-specific expression and regulation of the alternatively-spliced forms of lysyl hydroxylase 2 (LH2) in human kidney cells and skin fibroblasts.

Publication ,  Journal Article
Walker, LC; Overstreet, MA; Yeowell, HN
Published in: Matrix Biol
January 2005

Lysyl hydroxylases 1, 2, and 3 catalyse the hydroxylation of specific lysines in collagen. A small percentage of these hydroxylysine residues are precursors for the cross-link formation essential for the tensile strength of collagen. Lysyl hydroxylase 2 (LH2) exists as two alternatively-spliced forms; the long transcript (the major ubiquitously-expressed form) includes a 63 bp exon (13A) that is spliced out in the short form (expressed, together with the long form, in human kidney, spleen, liver, and placenta). This study shows that this alternative splicing event can be regulated by both cell density and cycloheximide (CHX). Although only the long form of LH2 is detected in untreated confluent human skin fibroblasts, after 24 h treatment with CHX the short LH2 transcript is also expressed. In kidney cells, in which both LH2 transcripts are equally expressed, the long LH2 transcript is significantly decreased after 24 h CHX treatment, whereas expression of the short transcript is slightly increased. This suggests that, in kidney cells, the splicing mechanism for the inclusion of exon 13A in LH2 requires a newly-synthesized protein factor that is suppressed by CHX, whereas, in skin fibroblasts in which levels of LH2 (long) are unaffected, CHX appears to suppress a factor that inhibits exclusion of exon 13A, thereby promoting expression of LH2 (short). As these alternate transcripts of LH2 may have specificity for hydroxylation of lysines in either telopeptide or helical collagen domains, their relative expression determines the type of cross-links formed, thereby affecting collagen strength. Therefore, any perturbation of the regulation of LH2 splicing could influence the stability of the extracellular matrix and contribute to specific connective tissue disorders.

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Published In

Matrix Biol

DOI

ISSN

0945-053X

Publication Date

January 2005

Volume

23

Issue

8

Start / End Page

515 / 523

Location

Netherlands

Related Subject Headings

  • Tissue Distribution
  • Time Factors
  • Skin
  • RNA, Ribosomal, 18S
  • RNA, Messenger
  • Protein Synthesis Inhibitors
  • Protein Structure, Tertiary
  • Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase
  • Polymerase Chain Reaction
  • Models, Genetic
 

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Walker, L. C., Overstreet, M. A., & Yeowell, H. N. (2005). Tissue-specific expression and regulation of the alternatively-spliced forms of lysyl hydroxylase 2 (LH2) in human kidney cells and skin fibroblasts. Matrix Biol, 23(8), 515–523. https://doi.org/10.1016/j.matbio.2004.11.002
Walker, Linda C., Mayra A. Overstreet, and Heather N. Yeowell. “Tissue-specific expression and regulation of the alternatively-spliced forms of lysyl hydroxylase 2 (LH2) in human kidney cells and skin fibroblasts.Matrix Biol 23, no. 8 (January 2005): 515–23. https://doi.org/10.1016/j.matbio.2004.11.002.
Walker, Linda C., et al. “Tissue-specific expression and regulation of the alternatively-spliced forms of lysyl hydroxylase 2 (LH2) in human kidney cells and skin fibroblasts.Matrix Biol, vol. 23, no. 8, Jan. 2005, pp. 515–23. Pubmed, doi:10.1016/j.matbio.2004.11.002.
Journal cover image

Published In

Matrix Biol

DOI

ISSN

0945-053X

Publication Date

January 2005

Volume

23

Issue

8

Start / End Page

515 / 523

Location

Netherlands

Related Subject Headings

  • Tissue Distribution
  • Time Factors
  • Skin
  • RNA, Ribosomal, 18S
  • RNA, Messenger
  • Protein Synthesis Inhibitors
  • Protein Structure, Tertiary
  • Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase
  • Polymerase Chain Reaction
  • Models, Genetic