Loricrin at the Boundary between Inside and Outside

Abstract

Cornification is a specialized mode of the cell-death program, exclusively, and is allowed for terrestrial amniotes. Recent investigations suggest that loricrin (LOR) is an important cornification effector. As the connotation of its name (“lorica” meaning an armor in Latin) suggests, the keratin-associated protein LOR promotes the maturation of the epidermal structure through organizing covalent cross-linkages, endowing the epidermis with the protection against oxidative injuries. By reviewing cornification mechanisms, we seek to classify ichthyosiform dermatoses based on their function, rather than clinical manifestations. We also reviewed recent mechanistic insights into the Kelch-like erythroid cell-derived protein with the cap “n” collar homology-associated protein 1/nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway in skin health and diseases, as LOR and NRF2 coordinate the epidermis-intrinsic xenobiotic metabolism. Finally, we refine the theoretical framework of cross-talking between keratinocytes and epidermal resident leukocytes, dissecting an LOR immunomodulatory function.

Transcriptomics analysis reveals molecular alterations underpinning spaceflight dermatology

“…During conversion of keratinocyte cell membrane to cornified cell envelope, filaggrin aggregates and aligns intermediate filaments such as keratin 1 and keratin 10, within the cytoskeleton of keratinocytes, and subsequently a cross-linking process is initiated by proteins such as involucrin and locicrin 108 , 109 . This results in compactization and flattening of the corneocytes, one of the constituents of the skin barrier 110 . We identified FLG as one of the cross-mission genes in the spaceflight vs ground control mice data with downregulation across the majority of data subsets (all except RR-5 dorsal skin) (Fig.…”

Skin Ageing: A Progressive, Multi-Factorial Condition Demanding an Integrated, Multilayer-Targeted Remedy

“… 66 Furthermore, the effort to improve epidermal barrier is worth via increasing expressions of “cornified envelope”-related proteins such as keratin, 67 filaggrin, 68 and loricrin. 69 …”

NRF2 in the Epidermal Pigmentary System

“…Compared with pigmentation in the hair, tanning responses (IFE melanogenesis) depend on the nature of differentiated McSC-derived melanocytes; wet-surfaced SE (squamous mucosa), palmoplantar epidermis, or its apparatus (the nail) hardly experiences tanning responses (caused by the predominance of eumelanogenesis over pheomelanogenesis). The "niche" instruction or "structural imprinting" [138] aspect of pigmentogenesis would be further rationalized when IFE differentiation is analogized to sulfur metabolism; thiol groups of the proliferative layer are converted to disulfide polymerized keratins [139] (Figure 2). The principle, along with the possibility that the eumelanin synthetic pathway is regulated post-transcriptionally [35], tempted us to determine the "niche factor" within the IFE component.…”