Autoantikehad täppismeditsiinis

Immuuntolerantsi häirumine, mille üheks väljundiks on antikehade teke organismile omaste biomolekulide vastu, on oluline patogeneetiline mehhanism mitmete laialdaselt levinud haiguste puhul ja seetõttu on autoantikehade määramine kujunenud oluliseks diagnostiliseks vahendiks. Artiklis on käsitletud autoantikehade esinemise olulisust haiguste tekke ja kulu prognoosimisel. Kuigi sellekohane info on veel üsna napp, on selge, et organismi immuunstaatuse muutus eelneb aastaid haiguse ilmnemisele ning autoimmuunset komponenti sisaldava haiguse kulg ja prognoos on seotud patsiendil esinevate kindlate autoantikehadega. Sellest tulenevalt võime loota, et organismi immuunstaatuse uurimine, eriti aga autoantikehade spektri iseloomustamine, on tulevikus geneetilise info analüüsimise kõrval üks täppismeditsiini olulisemaid tööriistu

Hidradenitis suppurativa – mädane higinäärmepõletik

Mädane higinäärmepõletik ehk hidradenitis suppurativa (HS) on krooniline, ägenemiste ja remissioonidega kulgev ning organismi nõrgestav põletikuline nahahaigus, mis lisaks nahakahjustusele võib tekitada märgatavaid psühhosotsiaalseid vaevusi. Kuna selle haiguse kliiniline pilt on varieeruv ning haigus haarab sageli intiimpiirkondi, võib diagnoos hilineda aastaid. Artiklis on käsitletud selle ilmselt aladiagnoositud haiguse olemust, kliinilist pilti ning ravivõimalusi

Hidradenitis suppurativa – mädane higinäärmepõletik

Mädane higinäärmepõletik ehk hidradenitis suppurativa (HS) on krooniline, ägenemiste ja remissioonidega kulgev ning organismi nõrgestav põletikuline nahahaigus, mis lisaks nahakahjustusele võib tekitada märgatavaid psühhosotsiaalseid vaevusi. Kuna selle haiguse kliiniline pilt on varieeruv ning haigus haarab sageli intiimpiirkondi, võib diagnoos hilineda aastaid. Artiklis on käsitletud selle ilmselt aladiagnoositud haiguse olemust, kliinilist pilti ning ravivõimalusi

Primary Ciliary Signaling in the Skin—Contribution to Wound Healing and Scarring

Primary cilia (PC) are solitary, post-mitotic, microtubule-based, and membrane-covered protrusions that are found on almost every mammalian cell. PC are specialized cellular sensory organelles that transmit environmental information to the cell. Signaling through PC is involved in the regulation of a variety of cellular processes, including proliferation, differentiation, and migration. Conversely, defective, or abnormal PC signaling can contribute to the development of various pathological conditions. Our knowledge of the role of PC in organ development and function is largely based on ciliopathies, a family of genetic disorders with mutations affecting the structure and function of PC. In this review, we focus on the role of PC in their major signaling pathways active in skin cells, and their contribution to wound healing and scarring. To provide comprehensive insights into the current understanding of PC functions, we have collected data available in the literature, including evidence across cell types, tissues, and animal species. We conclude that PC are underappreciated subcellular organelles that significantly contribute to both physiological and pathological processes of the skin development and wound healing. Thus, PC assembly and disassembly and PC signaling may serve as attractive targets for antifibrotic and antiscarring therapies.Peer reviewe

Matricellular proteins in cutaneous wound healing

Cutaneous wound healing is a complex process that encompasses alterations in all aspects of the skin including the extracellular matrix (ECM). ECM consist of large structural proteins such as collagens and elastin as well as smaller proteins with mainly regulative properties called matricellular proteins. Matricellular proteins bind to structural proteins and their functions include but are not limited to interaction with cell surface receptors, cytokines, or protease and evoking a cellular response. The signaling initiated by matricellular proteins modulates differentiation and proliferation of cells having an impact on the tissue regeneration. In this review we give an overview of the matricellular proteins that have been found to be involved in cutaneous wound healing and summarize the information known to date about their functions in this process.Peer reviewe

Case Report: Unravelling the Mysterious Lichtenberg Figure Skin Response in a Patient With a High-Voltage Electrical Injury

cited By 0We describe a case of Lichtenberg Figures (LFs) following an electrical injury from a high-voltage switchgear in a 47 year-old electrician. LFs, also known as ferning pattern or keraunographic markings, are a pathognomonic skin sign for lightning strike injuries. Their true pathophysiology has remained a mystery and only once before described following an electical injury. The aim was to characterise the tissue response of LFs by performing untargeted non-labelled proteomics and immunohistochemistry on paraffin-embedded sections of skin biopsies taken from the area of LFs at presentation and at 3 months follow-up. Our results demonstrated an increase in dermal T-cells and greatly increased expression of the iron-binding glycoprotein lactoferrin by keratinocytes and lymphocytes. These changes in the LF-affected skin were associated with extravasation of red blood cells from dermal vessels. Our results provide an initial molecular and cellular insight into the tissue response associated with LFs.Peer reviewe

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

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.Peer reviewe

Melanocytes in the Skin - Comparative Whole Transcriptome Analysis of Main Skin Cell Types (vol 9, e115717, 2014)

[This corrects the article DOI: 10.1371/journal.pone.0115717.]

Olfactomedin-4 improves cutaneous wound healing by promoting skin cell proliferation and migration through POU5F1/OCT4 and ESR1 signalling cascades

Olfactomedin-4 (OLFM4) is an olfactomedin-domain-containing glycoprotein, which regulates cell adhesion, proliferation, gastrointestinal inflammation, innate immunity and cancer metastasis. In the present study we investigated its role in skin regeneration. We found that OLFM4 expression is transiently upregulated in the proliferative phase of cutaneous wound healing in humans as well as in mice. Moreover, a significant increase in OLFM4 expression was detected in the skin of lesional psoriasis, a chronic inflammatory disease characterized by keratinocyte hyperproliferation. In vitro experiments demonstrated that OLFM4 selectively stimulated keratinocyte proliferation and increased both keratinocyte and fibroblast migration. Using proteotranscriptomic pathway analysis we revealed that transcription factors POU5F1/OCT4 and ESR1 acted as hubs for OLFM4-induced signalling in keratinocytes. In vivo experiments utilizing mouse splinted full-thickness cutaneous wound healing model showed that application of recombinant OLFM4 protein can significantly improve wound healing efficacy. Taken together, our results suggest that OLFM4 acts as a transiently upregulated inflammatory signal that promotes wound healing by regulating both dermal and epidermal cell compartments of the skin.Peer reviewe

Stimulation with THBS4 activates pathways that regulate proliferation, migration and inflammation in primary human keratinocytes

As in other mammalian tissues, the extracellular matrix (ECM) of skin functions as mechanical support and regulative environment that guides the behavior of the cells. ECM is a gel-like structure that is primarily composed of structural and nonstructural proteins. While the content of structural proteins is stable, the level of nonstructural ECM proteins, such as thrombospondin-4 (THBS4), is dynamically regulated. In a previous work we demonstrated that THBS4 stimulated cutaneous wound healing. In this work we discovered that in addition to proliferation, THBS4 stimulated the migration of primary keratinocytes in 3D. By using a proteotransciptomic approach we found that stimulation of keratinocytes with THBS4 regulated the activity of signaling pathways linked to proliferation, migration, inflammation and differentiation. Interestingly, some of the regulated genes (eg IL37, TSLP) have been associated with the pathogenesis of atopic dermatitis (AD). We concluded that THBS4 is a promising candidate for novel wound healing therapies and suggest that there is a potential convergence of pathways that stimulate cutaneous wound healing with those active in the pathogenesis of inflammatory skin diseases.(c) 2022 Published by Elsevier Inc.Peer reviewe