Discovery of increased epidermal DNAH10 expression after regeneration of dermis in a randomized with-in person trial \u2014 reflections on psoriatic inflammation

Outi Elomaa,Juha Kere,Viljar Jaks,Mariliis Klaas,Heli Lagus,Susanna Juteau,Jyrki Vuola,Esko Kankuri

doi:10.1038/s41598-019-53874-z

Abstract

Because molecular memories of past inflammatory events can persist in epidermal cells, we evaluated the long-term epidermal protein expression landscapes after dermal regeneration and in psoriatic inflammation. We first characterized the effects of two dermal regeneration strategies on transplants of indicator split-thickness skin grafts (STSGs) in ten adult patients with deep burns covering more than 20% of their body surface area. After fascial excision, three adjacent areas within the wound were randomized to receive a permanent dermal matrix, a temporary granulation-tissue-inducing dressing or no dermal component as control. Control areas were covered with STSG immediately, and treated areas after two-weeks of dermis formation. Epidermis-dermis-targeted proteomics of one-year-follow-up samples were performed for protein expression profiling. Epidermal expression of axonemal dynein heavy chain 10 (DNAH10) was increased 20-fold in samples having had regenerating dermis vs control. Given the dermal inflammatory component found in our dermal regeneration samples as well as in early psoriatic lesions, we hypothesized that DNAH10 protein expression also would be affected in psoriatic skin samples. We discovered increased DNAH10 expression in inflammatory lesions when compared to unaffected skin. Our results associate DNAH10 expression with cell proliferation and inflammation as well as with the epidermal memory resulting from the previous regenerative signals of dermis. This study (ISRCTN14499986) was funded by the Finnish Ministry of Defense and by government subsidies for medical research.

Highlights

Cellular and molecular interactions in the skin are crucial for preserving structure and functionality of the epidermis, the skin’s outer boundary to the external world[1]
We extend our results to a pathological perspective of dermal inflammation in skin samples collected from lesional and non-lesional sites of psoriatic skin, as well as from healthy control skin[27,28]
We discovered greatly increased expression of a dynein protein, dynein heavy chain 10 (DNAH10), in epidermis predisposed to an active dermal component

Summary

Introduction

Cellular and molecular interactions in the skin are crucial for preserving structure and functionality of the epidermis, the skin’s outer boundary to the external world[1]. Epidermal cells undergo a coordinated process of differentiation and apoptosis as they migrate to their demise, from the basement membrane separating epidermis from the underlying dermis[2,3,4]. The dermis, rich in extracellular matrix, nerves, and vasculature, nurtures the epidermis from below and produces critical paracrine signals to assist maintenance and regulation of epidermal structure and homeostasis[6,7,8,9]. Epidermal cells utilize highly conserved membranous structures, such as the primary cilia, to translate these signals for control of critical cellular responses e.g., proliferation, migration, and differentiation[16,17,18,19]. Very little is known about epidermal responses and molecular memory after regeneration of the entire dermis in humans. We extend our results to a pathological perspective of dermal inflammation in skin samples collected from lesional and non-lesional sites of psoriatic skin, as well as from healthy control skin[27,28]

Methods

Results

Conclusion