Chromatin architectural protein CTCF controls terminal keratinocyte differentiation, epidermal barrier maintenance and suppresses inflammatory responses in the skin

2017 ◽  
Author(s):  
Igor Malashchuk
Keyword(s):  
Inflammatory Responses ◽  
Keratinocyte Differentiation ◽  
Epidermal Barrier ◽  
Architectural Protein

scholarly journals The Role of MicroRNAs in Epidermal Barrier

2020 ◽  
Vol 21 (16) ◽  
pp. 5781
Author(s):  
Ai-Young Lee
Keyword(s):  
Cell Adhesion ◽  
Critical Role ◽  
Keratinocyte Differentiation ◽  
Epidermal Barrier ◽  
Barrier Integrity ◽  
Skin Lipids ◽  
Differentiation And Proliferation ◽  
The Impact ◽  
Cell Cell

MicroRNAs (miRNAs), which mostly cause target gene silencing via transcriptional repression and degradation of target mRNAs, regulate a plethora of cellular activities, such as cell growth, differentiation, development, and apoptosis. In the case of skin keratinocytes, the role of miRNA in epidermal barrier integrity has been identified. Based on the impact of key genetic and environmental factors on the integrity and maintenance of skin barrier, the association of miRNAs within epidermal cell differentiation and proliferation, cell–cell adhesion, and skin lipids is reviewed. The critical role of miRNAs in the epidermal barrier extends the use of miRNAs for control of relevant skin diseases such as atopic dermatitis, ichthyoses, and psoriasis via miRNA-based technologies. Most of the relevant miRNAs have been associated with keratinocyte differentiation and proliferation. Few studies have investigated the association of miRNAs with structural proteins of corneocytes and cornified envelopes, cell–cell adhesion, and skin lipids. Further studies investigating the association between regulatory and structural components of epidermal barrier and miRNAs are needed to elucidate the role of miRNAs in epidermal barrier integrity and their clinical implications.

scholarly journals Fucoidan from Undaria pinnatifida Ameliorates Epidermal Barrier Disruption via Keratinocyte Differentiation and CaSR Level Regulation

Marine Drugs ◽  
2019 ◽  
Vol 17 (12) ◽  
pp. 660
Author(s):  
Yu Chen ◽  
Xuenan Li ◽  
Xiaoshuang Gan ◽  
Junmei Qi ◽  
Biao Che ◽  
...  
Keyword(s):  
Undaria Pinnatifida ◽  
Keratinocyte Differentiation ◽  
Mechanistic Study ◽  
Calcium Sensing Receptor ◽  
Epidermal Barrier ◽  
Barrier Disruption ◽  
Calcium Sensing ◽  
External Agents ◽  
Proliferation And Differentiation ◽  
Barrier Repair

The epidermal barrier acts as a line of defense against external agents as well as helps to maintain body homeostasis. The calcium concentration gradient across the epidermal barrier is closely related to the proliferation and differentiation of keratinocytes (KCs), and the regulation of these two processes is the key to the repair of epidermal barrier disruption. In the present study, we found that fucoidan from Undaria pinnatifida (UPF) could promote the repair of epidermal barrier disruption in mice. The mechanistic study demonstrated that UPF could promote HaCaT cell differentiation under low calcium condition by up-regulating the expression of calcium-sensing receptor (CaSR), which could then lead to the activation of the Catenin/PLCγ1 pathway. Further, UPF could increase the expression of CaSR through activate the ERK and p38 pathway. These findings reveal the molecular mechanism of UPF in the repair of the epidermal barrier and provide a basis for the development of UPF into an agent for the repair of epidermal barrier repair.

scholarly journals Caspase-14 reveals its secrets

2008 ◽  
Vol 180 (3) ◽  
pp. 451-458 ◽  
Author(s):  
Geertrui Denecker ◽  
Petra Ovaere ◽  
Peter Vandenabeele ◽  
Wim Declercq
Keyword(s):  
Current Knowledge ◽  
Keratinocyte Differentiation ◽  
Uvb Radiation ◽  
Epidermal Barrier ◽  
Unique Member ◽  
Evolutionarily Conserved ◽  
Proliferation And Differentiation ◽  
Deficient Mice

Caspase-14 is a unique member of the evolutionarily conserved family of cysteinyl aspartate–specific proteinases, which are mainly involved in inflammation and apoptosis. However, recent evidence also implicates these proteases in proliferation and differentiation. Although most caspases are ubiquitously expressed, caspase-14 expression is confined mainly to cornifying epithelia, such as the skin. Moreover, caspase-14 activation correlates with cornification, indicating that it plays a role in terminal keratinocyte differentiation. The determination of in vitro conditions for caspase-14 activity paved the way to identifying its substrates. The recent development of caspase-14–deficient mice underscored its importance in the correct degradation of (pro)filaggrin and in the formation of the epidermal barrier that protects against dehydration and UVB radiation. Here, we review the current knowledge on caspase-14 in skin homeostasis and disease.

scholarly journals Integrin-Linked Kinase Is Indispensable for Keratinocyte Differentiation and Epidermal Barrier Function

2016 ◽  
Vol 136 (2) ◽  
pp. 425-435 ◽  
Author(s):  
Samar Sayedyahossein ◽  
Alena Rudkouskaya ◽  
Valerie Leclerc ◽  
Lina Dagnino
Keyword(s):  
Barrier Function ◽  
Keratinocyte Differentiation ◽  
Epidermal Barrier ◽  
Integrin Linked Kinase

scholarly journals Epidermal ADAM17 maintains the skin barrier by regulating EGFR ligand–dependent terminal keratinocyte differentiation

2012 ◽  
Vol 209 (6) ◽  
pp. 1105-1119 ◽  
Author(s):  
Claus-Werner Franzke ◽  
Cristina Cobzaru ◽  
Antigoni Triantafyllopoulou ◽  
Stefanie Löffek ◽  
Keisuke Horiuchi ◽  
...  
Keyword(s):  
Immune Cell ◽  
Tissue Injury ◽  
Critical Role ◽  
Growth Factor Receptor ◽  
Skin Barrier ◽  
Skin Inflammation ◽  
Transepidermal Water Loss ◽  
Epidermal Differentiation ◽  
Keratinocyte Differentiation ◽  
Epidermal Barrier

ADAM17 (a disintegrin and metalloproteinase 17) is ubiquitously expressed and cleaves membrane proteins, such as epidermal growth factor receptor (EGFR) ligands, l-selectin, and TNF, from the cell surface, thus regulating responses to tissue injury and inflammation. However, little is currently known about its role in skin homeostasis. We show that mice lacking ADAM17 in keratinocytes (A17ΔKC) have a normal epidermal barrier and skin architecture at birth but develop pronounced defects in epidermal barrier integrity soon after birth and develop chronic dermatitis as adults. The dysregulated expression of epidermal differentiation proteins becomes evident 2 d after birth, followed by reduced transglutaminase (TGM) activity, transepidermal water loss, up-regulation of the proinflammatory cytokine IL-36α, and inflammatory immune cell infiltration. Activation of the EGFR was strongly reduced in A17ΔKC skin, and topical treatment of A17ΔKC mice with recombinant TGF-α significantly improved TGM activity and decreased skin inflammation. Finally, we show that mice lacking the EGFR in keratinocytes (EgfrΔKC) closely resembled A17ΔKC mice. Collectively, these results identify a previously unappreciated critical role of the ADAM17–EGFR signaling axis in maintaining the homeostasis of the postnatal epidermal barrier and suggest that this pathway could represent a good target for treatment of epidermal barrier defects.

scholarly journals miR-155 Contributes to Normal Keratinocyte Differentiation and Is Upregulated in the Epidermis of Psoriatic Skin Lesions

2020 ◽  
Vol 21 (23) ◽  
pp. 9288
Author(s):  
Lucian Beer ◽  
Polina Kalinina ◽  
Martin Köcher ◽  
Maria Laggner ◽  
Markus Jeitler ◽  
...  
Keyword(s):  
Skin Diseases ◽  
Normal Skin ◽  
Skin Lesions ◽  
Keratinocyte Differentiation ◽  
Psoriatic Skin ◽  
Bioinformatics Analyses ◽  
Epidermal Barrier ◽  
Barrier Formation

The role of microRNAs (miRNAs) during keratinocyte (KC) differentiation and in skin diseases with epidermal phenotypes has attracted strong interest over the past few years. However, combined mRNA and miRNA expression analyses to elucidate the intricate mRNA–miRNA networks of KCs at different stages of differentiation have not been performed yet. In the present study, we investigated the dynamics of miRNA and mRNA expression during KC differentiation in vitro and in normal and psoriatic epidermis. While we identified comparable numbers of up- and downregulated mRNAs (49% and 51%, respectively), miRNAs were predominantly upregulated (76% vs 24%) during KC differentiation. Further bioinformatics analyses suggested an important inhibitory role for miR-155 in KC differentiation, as it was repressed during KC differentiation in normal skin but strongly upregulated in the epidermis of psoriatic skin lesions. Mimicking the inflammatory milieu of psoriatic skin in vitro, we could show that the pro-inflammatory cytokines IL17, IL1β and INFγ synergistically upregulated miR-155 expression in KCs. Forced over-expression of miR-155 in human in vitro skin models specifically reduced the expression of loricrin (LOR) in KCs, indicating that miR-155 interferes with the establishment of a normal epidermal barrier. Together, our data indicate that downregulation of miR-155 during KC differentiation is a crucial step for epidermal barrier formation. Furthermore, its strong upregulation in psoriatic lesions suggests a contributing role of miR-155 in the altered keratinocyte differentiation observed in psoriasis. Therefore, miR-155 represents as a potential target for treating psoriatic skin lesions.

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