Overhydroxylation of Lysine of Collagen Increases Uterine Fibroids Proliferation

Roles of Lysyl Hydroxylases, Lysyl Oxidases, and Matrix Metalloproteinases

Marwa Kamel, Mohamed Wagih, Gokhan Kilic, Concepcion R. Diaz-Arrastia, Mohamed A. Baraka, Salama A. Salama

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The role of the extracellular matrix (ECM) in uterine fibroids (UF) has recently been appreciated. Overhydroxylation of lysine residues and the subsequent formation of hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) cross-links underlie the ECM stiffness and profoundly affect tumor progression. The aim of the current study was to investigate the relationship between ECM of UF, collagen and collagen cross-linking enzymes [lysyl hydroxylases (LH) and lysyl oxidases (LOX)], and the development and progression of UF. Our results indicated that hydroxyl lysine (Hyl) and HP cross-links are significantly higher in UF compared to the normal myometrial tissues accompanied by increased expression of LH (LH2b) and LOX. Also, increased resistance to matrix metalloproteinases (MMP) proteolytic degradation activity was observed. Furthermore, the extent of collagen cross-links was positively correlated with the expression of myofibroblast marker (α-SMA), growth-promoting markers (PCNA; pERK1/2; FAKpY397; Ki-67; and Cyclin D1), and the size of UF. In conclusion, our study defines the role of overhydroxylation of collagen and collagen cross-linking enzymes in modulating UF cell proliferation, differentiation, and resistance to MMP. These effects can establish microenvironment conducive for UF progression and thus represent potential target treatment options of UF.

Original languageEnglish (US)
Article number5316845
JournalBioMed Research International
Volume2017
DOIs
StatePublished - 2017

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2-Oxoglutarate 5-Dioxygenase Procollagen-Lysine
Protein-Lysine 6-Oxidase
Leiomyoma
Matrix Metalloproteinases
Lysine
Collagen
Extracellular Matrix
Cyclin D1
Proliferating Cell Nuclear Antigen
Cell proliferation
Stiffness matrix
Enzymes
Hydroxyl Radical
Tumors
Myofibroblasts
Tissue
Degradation
Cell Differentiation
Cell Proliferation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Overhydroxylation of Lysine of Collagen Increases Uterine Fibroids Proliferation : Roles of Lysyl Hydroxylases, Lysyl Oxidases, and Matrix Metalloproteinases. / Kamel, Marwa; Wagih, Mohamed; Kilic, Gokhan; Diaz-Arrastia, Concepcion R.; Baraka, Mohamed A.; Salama, Salama A.

In: BioMed Research International, Vol. 2017, 5316845, 2017.

Research output: Contribution to journalArticle

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abstract = "The role of the extracellular matrix (ECM) in uterine fibroids (UF) has recently been appreciated. Overhydroxylation of lysine residues and the subsequent formation of hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) cross-links underlie the ECM stiffness and profoundly affect tumor progression. The aim of the current study was to investigate the relationship between ECM of UF, collagen and collagen cross-linking enzymes [lysyl hydroxylases (LH) and lysyl oxidases (LOX)], and the development and progression of UF. Our results indicated that hydroxyl lysine (Hyl) and HP cross-links are significantly higher in UF compared to the normal myometrial tissues accompanied by increased expression of LH (LH2b) and LOX. Also, increased resistance to matrix metalloproteinases (MMP) proteolytic degradation activity was observed. Furthermore, the extent of collagen cross-links was positively correlated with the expression of myofibroblast marker (α-SMA), growth-promoting markers (PCNA; pERK1/2; FAKpY397; Ki-67; and Cyclin D1), and the size of UF. In conclusion, our study defines the role of overhydroxylation of collagen and collagen cross-linking enzymes in modulating UF cell proliferation, differentiation, and resistance to MMP. These effects can establish microenvironment conducive for UF progression and thus represent potential target treatment options of UF.",
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AU - Baraka, Mohamed A.

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