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Overhydroxylation of Lysine of Collagen Increases Uterine Fibroids Proliferation: Roles of LysylHydroxylases, Lysyl Oxidases, and Matrix Metalloproteinases.
PubMed
Kamel, Marwa; Wagih, Mohamed; Kilic, Gokhan S; Diaz-Arrastia, Concepcion R; Baraka, Mohamed A; Salama, Salama A
2017-01-01
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 [lysylhydroxylases (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; FAK pY397 ; 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.
Overhydroxylation of Lysine of Collagen Increases Uterine Fibroids Proliferation: Roles of LysylHydroxylases, Lysyl Oxidases, and Matrix Metalloproteinases
PubMed Central
Kamel, Marwa; Wagih, Mohamed; Diaz-Arrastia, Concepcion R.; Baraka, Mohamed A.
2017-01-01
The role of the extracellular matrix (ECM) in uterine f OLUSEYI AJAYI 2013 are delighted to welcome you to the 27th annual BAM conference. The conference theme 'managing to make a difference' invites Academy members to reflect on whether and how we can make a difference. Faced with the increased demand to justify academic work in times of austerity and under the impress of a number of major managerial failures with far-reaching effects for employees, investors and society at large, questions related to the contribution of academic work in business and management have become immensely important. At the same time, however, we have witnessed a growing body of actionable knowledge, innovative teaching pedagogies, and critical reflections which demonstrates the vibrancy of intellectual contributions to business and management. We have also received record numbers of submissions to this year's conference indicating that the Academy is full of life and capable of doing more than just 'managing' to make a difference. The BAM conference continues to provide a format for challenging discussions and we are delighted to announce a diverse portfolio of conference tracks, paper development workshops and a highly popular doctoral symposium. We commence our discussions with a plenary speech by Professor Roy Suddaby, editor of the Academy of Management Review. Roy is a leading figure in reconsidering the importance of 'work' in institutional theory which is closely concerned with questions of how we can make a difference. However, as the ancient Greeks already knew, the discussion of serious ideas is best done in in the format of a symposium which combines the intellectual with the social. We there .Liste von Pseudonymen
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