Reciprocal regulation of LOX and LOXL2 expression during cell adhesion and terminal differentiation in epidermal keratinocytes

Fujimoto, Eita; Tajima, S.

doi:10.1016/j.jdermsci.2009.03.010

Cited by 16 publications

(22 citation statements)

References 52 publications

(63 reference statements)

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“…In contrast, knocking-down LOX does not affect collagen IV assembly. Indeed, several lines of evidence support that LOXL2, rather than LOX, is responsible for collagen IV assembly and cross-linking: (Ϫ1) Unlike LOXL2, LOX is not colocalized with collagen IV in hypoxic HUVECs (data not shown); (Ϫ2) the complementary distribution of LOX and LOXL2 in cells that generate the interstitial ECM or that deposit basement membrane, respectively, was reported in the epidermis and placenta 33,34 ; (Ϫ3) collagen IV up-regulates LOXL2 expression and exerts opposite effects on LOX 33 ; (Ϫ4) there is no modification of collagen IV deposition nor of basement membrane organization in LOX knockout mice, whereas fibrillar collagen organization is altered 36 ; in contrast, LOXL2 knockdown does not affect deposition of collagen I. 10 We found that inhibiting LOXL2 cross-linking activity did not affect collagen IV assembly.…”

Section: Discussionmentioning

confidence: 95%

“…LOXL2 expression had already been reported in other cells that deposit basement membrane. 12,33,34 LOXL2 could thus be the member of the lysyl oxidase family more specifically targeted to basement membranes and dedicated to cross-linking the nonfibrillar collagen IV. Lysyl oxidase-mediated crosslinks are located in the 7S domain of collagen IV, but the lysyl oxidase responsible is not identified yet.…”

Section: Discussionmentioning

confidence: 99%

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Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV collagen assembly in the endothelial basement membrane

Bignon

Pichol-Thievend

Hardouin

et al. 2011

Blood

170

173

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Sprouting angiogenesis is associated with extensive extracellular matrix (ECM) remodeling. The molecular mechanisms involved in building the vascular microenvironment and its impact on capillary formation remain elusive. We therefore performed a proteomic analysis of ECM from endothelial cells maintained in hypoxia, a major stimulator of angiogenesis. Here, we report the characterization of lysyl oxidase-like protein-2 (LOXL2) as a hypoxia-target expressed in neovessels and accumulated in the endothelial ECM. IntroductionAngiogenesis occurs during development and tissue remodeling, and in the pathologic context of cardiovascular ischemic diseases or tumor growth. Sprouting of new vessels is initiated by stimulation of endothelial cells (ECs) by a combination of signals from the microenvironment that includes oxygen tension and growth factors. Cells from not yet vascularized tissue and ECs that invade this microenvironment are both hypoxia targets through the Hypoxia Inducible Factor (HIF) pathway. HIF activates transcription of genes coding for autocrine/paracrine factors like vascular endothelial growth factor (VEGF) and extracellular matrix (ECM) components. 1 Synergy between these responses is assumed through local concentration of growth factors in the ECM where they function as attractant for ECs. Specialized ECs, called tip cells, lead vascular growth by sending out filopodia to explore the hypoxic microenvironment. 2 Tip cells are thus continuously exposed to low oxygen concentration. 3 Stalk cells, located behind the tip cells, serve to vessel growth by proliferation, lumen formation and junction establishment. 4 Vascular ECM undergoes major remodeling during angiogenesis, consisting in ECM/basement membrane degradation, provisional ECM generation and assembly of a new basement membrane. ECM-mediated mechanotransductive signaling regulates 3D multicellular organization, including lumen formation and tubulogenesis. Thus, in addition to storing angiogenic factors and providing structural features, ECM is a dynamic promoter of angiogenesis. 5 Subendothelial basement membrane is composed of nonfibrillar collagen IV, laminin, perlecan and nidogens. Other collagens (VIII, XV, and XVIII), fibronectin and matricellular proteins (thrombospondin-1, Cyr61) are associated with the basement membrane. There is only little data concerning the assembly of the vascular microenvironment and its impact on angiogenesis. Genes encoding ECM components and enzymes involved in their assembly and stabilization are targets of hypoxia in ECs. 1 To identify key regulators of the angiogenesis-associated ECM remodeling, we performed a proteomic analysis of endothelial ECM generated in vitro under hypoxic conditions. We found that the ECM cross-linking enzyme, lysyl oxidase-like protein-2 (LOXL2) is a major target of hypoxia. Lysyl oxidases, consisting in lysyl oxidase (LOX) and 4 lysyl oxidase-like proteins (LOXL 1 to 4), catalyze the deamination of lysines and hydroxylysines, generating aldehydes that spontaneously react to form co...

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV collagen assembly in the endothelial basement membrane

Bignon

Pichol-Thievend

Hardouin

et al. 2011

Blood

170

173

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“…Silencing LOXL2 expression in keratinocytes up-regulates the expression of genes associated with keratinocyte differentiation (16), suggesting that the LOXL2 overexpression observed in squamous cell carcinomas may contribute to tumor progression either through inhibition of the differentiation of keratinocyte-derived tumor cells or through enhancement of their proliferation, which in turn inhibits differentiation (13). Interestingly, the expression of LOX and LOXL2 is inversely regulated in keratinocytes as a function of their state of differentiation even though both enzymes catalyze similar enzymatic reactions and even though both oxidize lysine residues of collagen (2, 7).…”

Section: Lysyl Oxidase-like-2 (Loxl2) Induces Tumor Progression and Fmentioning

confidence: 99%

“…Interestingly, the expression of LOX and LOXL2 is inversely regulated in keratinocytes as a function of their state of differentiation even though both enzymes catalyze similar enzymatic reactions and even though both oxidize lysine residues of collagen (2, 7). Thus, LOX expression is induced in differentiating keratinocytes, whereas the expression of LOXL2 is inhibited (16). Furthermore, silencing LOX expression, in contrast to the silencing of LOXL2, impairs keratinocyte differentiation (17).…”

Section: Lysyl Oxidase-like-2 (Loxl2) Induces Tumor Progression and Fmentioning

confidence: 99%

The Enzymatic Activity of Lysyl Oxidas-like-2 (LOXL2) Is Not Required for LOXL2-induced Inhibition of Keratinocyte Differentiation

Lugassy

Zaffryar-Eilot

Soueid

et al. 2012

Journal of Biological Chemistry

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Background: LOXL2 inhibits keratinocyte differentiation. This activity was thought to require LOXL2 enzyme activity. Results: LOXL2 mutants lacking enzyme activity nevertheless inhibit keratinocyte differentiation. The fourth scavenger receptor-cysteine-rich domain of LOXL2 is required for this activity. Conclusion: LOXL2 induces keratinocyte differentiation independently of its enzyme activity. Significance: Our results suggest that LOXL2 may affect diverse biological processes independently of its enzyme activity.

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“…LOXL2 transcription, for instance, is downregulated during keratinocyte differentiation [171]. Concomitantly, the progression of skin squamous carcinoma cells (cells characterized by aberrant differentiation) is associated with enhanced LOXL2 expression [172].…”

Section: Loxl2 and Cellular Differentiationmentioning

confidence: 99%

Lysine-Specific Histone Demethylases Contribute to Cellular Differentiation and Carcinogenesis

Verde

Querol-Paños²,

Cebrià-Costa³

et al. 2017

Epigenomes

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Histone modifications regulate chromatin structure, gene transcription, and other nuclear processes. Among the histone modifications, methylation has been considered to be a stable, irreversible process due to the slow turnover of methyl groups in chromatin. However, the discovery of three different classes of lysine-specific demethylases-KDM1, Jumonji domain-containing demethylases, and lysyl oxidase-like 2 protein-has drastically changed this view, suggesting a role for dynamic histone methylation in different biological process. In this review, we describe the different mechanisms that these enzymes use to remove lysine histone methylation and discuss their role during physiological (cell differentiation) and pathological (carcinogenesis) processes.

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Reciprocal regulation of LOX and LOXL2 expression during cell adhesion and terminal differentiation in epidermal keratinocytes

Cited by 16 publications

References 52 publications

Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV collagen assembly in the endothelial basement membrane

Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV collagen assembly in the endothelial basement membrane

The Enzymatic Activity of Lysyl Oxidas-like-2 (LOXL2) Is Not Required for LOXL2-induced Inhibition of Keratinocyte Differentiation

Lysine-Specific Histone Demethylases Contribute to Cellular Differentiation and Carcinogenesis

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