Decreased lysyl oxidase-like 2 expression in mid-dermal elastolysis

Abstract

Mid-dermal elastolysis (MDE) is a rare disorder that is histopathologically characterized by selective loss of elastic fibres in the mid-dermis. Aetiopathogenesis of MDE is still obscure. We report for the first time on the expression of lysyl oxidase-like (LOXL) proteins in lesional and non-lesional skin of a patient with reticular variant of MDE. Real-time RT-PCR and immunohistochemistry were performed for matrix metalloproteinase-2 (MMP2), MMP7, MMP9, LOXL1, LOXL2, and LOXL3. LOXL1 and LOXL3 mRNA levels in lesional skin did not substantially differ from mRNA levels measured in healthy skin. For LOXL2, however, we found decreased mRNA expression in lesional skin as compared to healthy skin. mRNA expression of MMP2 and MMP7 of lesional skin did not substantially differ from healthy skin. However, MMP9 mRNA expression was massively increased in lesional skin when compared to healthy skin. Immunohistochemistry confirmed the altered expression of LOXL2 and MMP9 in lesional skin. In conclusion, our preliminary data suggest that not only increased elastolytic activity (e.g. MMP9 up-regulation) but also affected elastin renewal due to reduced LOXL expression may contribute to the pathogenesis of MDE. More research is warranted in MDE especially with regard to the LOX family, fibulins, fibrillins, and desmosines.

Lysyl oxidase-like 2 promoter hypermethylation in mid-dermal elastolysis

“…We have recently performed a case study demonstrating decreased mRNA and protein expression of LOXL2 in lesional skin of a patient with MDE . Thus we hypothesize that reduced LOXL2 expression in fibroblasts of MDE lesions may contribute to an additional reduction of the residual age‐related elastogenesis.…”

Mid-dermal elastolysis: A female-centric disease; case report and updated review of the literature

“…In addition to LOX, four LOX-like (LOXL) proteins have also been identified and play a role in biosynthesis and renewal of elastic tissue. Gambichler and Skrygan (2013) found increased MMP-9 expression decreased LOXL2 mRNA levels in lesional MDE skin.…”

“…Since Gambichler’s review in 2010, there have been 13 new publications regarding MDE, but these cover only 10 novel clinical cases, as Gambichler and colleagues wrote three distinct publications all regarding the same clinical patient (Gambichler and Skrygan, 2013, Gambichler et al, 2010, Scola et al, 2011). Furthermore, there were two publications on MDE that did not report new clinical cases (El-Khoury et al, 2014, Tong et al, 2013).…”

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

“…In addition to LOX, four LOX‐like proteins (LOXL1‐4) produced by the same gene family have been identified, which play a major role in biosynthesis and renewal of the elastic tissue . We recently published a case report showing that expression of LOXL2 is reduced in MDE . In the present study, we aimed to investigate LOXL2 expression in a larger sample of patients with MDE and to search for mutations in the gene LOXL2 .…”

“…5,6 We recently published a case report showing that expression of LOXL2 is reduced in MDE. 7 In the present study, we aimed to investigate LOXL2 expression in a larger sample of patients with MDE and to search for mutations in the gene LOXL2.…”