Lysyl oxidase-like-2 mutations and reduced mRNA and protein expression in mid-dermal elastolysis

Gambichler, Thilo; Mahjurian-Namari, M.; Reininghaus, L; Schmitz, Lutz; Skrygan, Marina; Schulze, H.‐J.; Schaller, Jörg; Girolomoni, Giampiero

doi:10.1111/ced.13652

Cited by 7 publications

(7 citation statements)

References 17 publications

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“…This hypothesis thus raises the possibility that LOXL2 participates in some steps of elastogenesis together with other LOXs. The recent identification of patients suffering from middermal elastolysis also supports the direct involvement of LOXL2 in the stability and maintenance of elastin ( 14 ).…”

Section: Discussionmentioning

confidence: 78%

“…The association of LOXL2 with ELN as a susceptibility gene for glaucoma was already proposed in Urban et al ( 34 ), but no functional interaction between these proteins was demonstrated in this study. More recently, the identification of LOXL2 mutations in patients suffering from middermal elastolysis directly raised the possibility that LOXL2 could participate in elastin cross-linking ( 14 ). We show here the direct binding of LOXL2 to TE using surface plasmon resonance, and we could detect lysine oxidation by recombinant LOXL2.…”

Section: Discussionmentioning

confidence: 99%

“…( 2 )]. The first patients carrying LOXL2 mutations were recently identified as suffering from middermal elastolysis ( 14 ), raising the possibility that LOXL2 could participate in elastin cross-linking. In the present study, we first determined the nanoscale structure of both full-length LOXL2 (FL-LOXL2) and a catalytic domain–deleted form that only comprises the 4 SRCR domains (SRCR14).…”

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confidence: 99%

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Lysyl oxidase‐like 2 (LOXL2)‐mediated cross‐linking of tropoelastin

et al. 2019

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Lysyl oxidases (LOXs) play a central role in extracellular matrix remodeling during development and tumor growth and fibrosis through cross-linking of collagens and elastin. We have limited knowledge of the structure and substrate specificity of these secreted enzymes. LOXs share a conserved C-terminal catalytic domain but differ in their N-terminal region, which is composed of 4 repeats of scavenger receptor cysteine-rich (SRCR) domains in LOX-like (LOXL) 2. We investigated by X-ray scattering and electron microscopy the low-resolution structure of the full-length enzyme and the structure of a shorter form lacking the catalytic domain. Our data demonstrate that LOXL2 has a rod-like structure with a stalk composed of the SRCR domains and the catalytic domain at its tip. We detected direct interaction between LOXL2 and tropoelastin (TE) and also LOXL2-mediated deamination of TE. Using proteomics, we identified several allysines together with cross-linked TE peptides. The elastin-like material generated was resistant to trypsin proteolysis and displayed mechanical properties similar to mature elastin. Finally, we detected the codistribution of LOXL2 and elastin in the vascular wall. Altogether, these data suggest that LOXL2 could participate in elastogenesis in vivo and could be used as a means of cross-linking TE in vitro for biomimetic and cell-compatible tissue engineering purposes.—Schmelzer, C. E. H., Heinz, A., Troilo, H., Lockhart-Cairns, M.-P., Jowitt, T. A., Marchand, M. F., Bidault, L., Bignon, M., Hedtke, T., Barret, A., McConnell, J. C., Sherratt, M. J., Germain, S., Hulmes, D. J. S., Baldock, C., Muller, L. Lysyl oxidase–like 2 (LOXL2)–mediated cross-linking of tropoelastin.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Lysyl oxidase‐like 2 (LOXL2)‐mediated cross‐linking of tropoelastin

et al. 2019

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“…La patogenia de la EDM no está bien comprendida pero se ha demostrado desequilibrio entre la activación exagerada de metaloproteinasas (MMP) de la matriz y una disminución en los inhibidores de elastasa que controlan la actividad catalítica, dando como resultado final pérdida de fibras elásticas 3,8 . Además se encontraron mutaciones en la enzima lisyl oxidasa, responsable de la formación de colágeno y elastina en la matriz extracelular 8,9 . La radiación ultravioleta es un cofactor de activación de MMP y es elevado el porcentaje de pacientes con antecedente de exposición solar previa al desarrollo de lesiones 2 .…”

Section: Comentariounclassified

Elastolisis de la dermis media: reporte de un caso

E¹,

González²,

Vidal³

et al. 2021

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La elastolisis de la dermis media (EDM) es una afección rara y adquirida del tejido elástico, caracterizada histológicamente por la disminución o ausencia de fibras elásticas en la porción media de la dermis. Afecta con mayor frecuencia a mujeres jóvenes, es asintomática y no se acompaña de compromiso extra cutáneo. Se presenta el caso de una paciente con finas arrugas en piel de ambas axilas y región lumbar.

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“…Lysyl oxidase-like 2 (LOXL2) is a member of the lysyl oxidase (LOX) gene family, which plays an important role in development, senescence, tumor suppression, cell growth, and chemotaxis [ 19 ]. LOXL2 catalyzes the oxidative deamination of the peptidyl lysine residues of extracellular matrix (ECM) proteins, such as, collagen and elastin, and promotes cross-linking of the ECM [ 20 , 21 ]. LOXL2 regulates angiogenesis by mediating collagen IV scaffolding [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

LOXL2 from human amniotic mesenchymal stem cells accelerates wound epithelialization by promoting differentiation and migration of keratinocytes

Zhao

Jiang

et al. 2020

Aging

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In this study, we identified wound healing-related proteins secreted by human amniotic epithelial cells (hAECs) and human amniotic mesenchymal stem cells (hAMSCs). We observed increased migration and reduced proliferation and differentiation when keratinocytes were co-cultured in media conditioned by hAECs (hAECs-CM) and hAMSCs (hAMSCs-CM). Label-free mass spectrometry and bioinformatic analyses of the hAECs-CM and hAMSCs-CM proteome revealed several proteins associated with wound healing, angiogenesis, cellular differentiation, immune response and cell motility. The levels of the proteins related to wound healing, including CTHRC1, LOXL2 and LGALS1, were significantly higher in hAMSCs-CM than hAECs-CM. LOXL2 significantly enhanced in vitro keratinocyte migration and differentiation compared to CTHRC1 and LGALS1. Moreover, LOXL2 enhanced keratinocyte migration and differentiation by activating the JNK signaling pathway. We observed significant reduction in the in vitro migration and differentiation of keratinocytes when co-cultured with medium conditioned by LOXL2-silenced hAMSCs and when treated with 10 μM SP600125, a specific JNK inhibitor. Treatment with hAMSCs-CM and LOXL2 significantly accelerated wound healing in the murine skin wound model. These findings show that LOXL2 promotes wound healing by inducing keratinocyte migration and differentiation via a JNK signaling pathway.

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Lysyl oxidase-like-2 mutations and reduced mRNA and protein expression in mid-dermal elastolysis

Abstract: Our present data suggest that decreased elastin renewal due to LOXL2 mutations and consecutive reduced LOXL2 expression contribute to the pathogenesis of MDE.

Cited by 7 publications

References 17 publications

Lysyl oxidase‐like 2 (LOXL2)‐mediated cross‐linking of tropoelastin

Lysyl oxidase‐like 2 (LOXL2)‐mediated cross‐linking of tropoelastin

Elastolisis de la dermis media: reporte de un caso

LOXL2 from human amniotic mesenchymal stem cells accelerates wound epithelialization by promoting differentiation and migration of keratinocytes

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