Abstract

Lysyl oxidase-like 2 (LOXL2) is a copper-dependent monoamine oxidase that contributes to the remodelling of the extracellular matrix (ECM) by cross linkage of collagen and elastin fibres and has emerged as a potential therapeutic target in cancer and fibrosis. In the skin, LOXL2 is essential for epidermal cell polarity and differentiation. However, its role in the dermis has not been evaluated. We found that Loxl2 is dispensable for mouse dermal development, maturation and homeostasis, yet affects dermal stiffness. Neither loss of Loxl2 nor increased Loxl2 expression affected dermal architecture following treatment with the phorbol ester TPA. Furthermore, Loxl2 expression did not alter the stroma of DMBA-TPA-induced tumours. We conclude that, although Loxl2 is expressed in both dermis and epidermis, its function appears largely confined to the epidermis.

Highlights

  • Lysyl oxidase-like 2 (LOXL2) belongs to the lysyl oxidase (LOX) protein family of copperdependent monoamine oxidases, which has five members, LOX and Lox-like (LOXL) LOXL1, 2, 3 and 4

  • Interrogation of published next-generation RNA sequencing data from mouse skin [24,25] established that, while all Lox family members are predominantly expressed in dermal fibroblasts, dermal papillae cells and melanocytes, Loxl2 is expressed by epithelial cells, as previously shown (Part A of S1 Fig) [12]

  • We confirmed expression of Lox family members by quantitative PCR (qPCR) of sorted GFP+ fibroblasts from PDGFRαH2BeGFP mice

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Summary

Introduction

Lysyl oxidase-like 2 (LOXL2) belongs to the lysyl oxidase (LOX) protein family of copperdependent monoamine oxidases, which has five members, LOX and Lox-like (LOXL) LOXL1, 2, 3 and 4. These proteins are secreted into the extracellular matrix (ECM) and their expression is tightly controlled during development [1]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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