Disease relevance of Lor

• Transgenic mice expressing a mutant form of loricrin reveal the molecular basis of the skin diseases, Vohwinkel syndrome and progressive symmetric erythrokeratoderma [1].
• Antinociceptive and antiedematogenic properties and acute toxicity of Tabebuia avellanedae Lor. ex Griseb. inner bark aqueous extract [2].
• Furthermore, in a chemical carcinogen-induced skin carcinogenesis setting, mice overexpressing human IKKalpha in the epidermis under the control of a truncated loricrin promoter developed significantly fewer SCCs and metastases than did wild-type mice [3].
• Skin targeted loricrin 8S-LOX/C57BL/6J transgenic mice showed a more differentiated epidermal phenotype as well as a 64% reduced papilloma development in a two-stage skin carcinogenesis protocol [4].

High impact information on Lor

• Identification of a major keratinocyte cell envelope protein, loricrin [5].
• Analysis of Skn-1a/i gene-deleted mice reveals that the Skn-1a/i gene modulates the pattern of expression of the terminal differentiation marker loricrin and inhibits expression of genes encoding markers of the epidermal keratinocyte wounding response [6].
• Finally, the skin of transgenic mice expressing a truncated loricrin promoter-driven dominant-negative TGFbeta type II receptor contained normal numbers of LC [7].
• At least one of the compensatory mechanisms preventing a more severe skin phenotype in newborn Lor(-/-) mice is an increase in the expression of other CE components, such as SPRRP2D and SPRRP2H, members of the family of "small proline rich proteins", and repetin, a member of the "fused gene" subgroup of the S100 gene family [8].
• A severe phenotype was observed in mice that lacked expression of wild-type loricrin [1].

Biological context of Lor

• This cell differentiation-specific expression pattern suggests specific suppression of loricrin gene expression in undifferentiated keratinocytes as well as its activation in differentiated keratinocytes [9].
• Constructs with point mutations in the putative YY1-binding motif showed increased reporter activity, indicating that YY1 negatively regulates loricrin gene transcription [9].
• In contrast to the dramatic repression of mRNAs typical for spinous cell differentiation, activation of PKC concurrently enhances expression of mRNAs and proteins for the granular cell markers loricrin and filaggrin [10].
• Transfection experiments indicated that the COOH-terminal domain of the mutant loricrin contains a nuclear localization signal [1].
• By analyses of RNA and protein, we show that the human transgene is expressed in mouse epithelial tissues in an appropriate developmental manner but at an overall level about twice that of endogenous mouse loricrin [11].

Anatomical context of Lor

• Loricrin is a major component of the epidermal cornified cell envelope, and is expressed only in terminally differentiated keratinocytes [9].
• These granules were first evident at E16 and the extrusion of lipids from the granules into the intercellular space occurred at E17, prior to the cross linking of loricrin into the cell envelope [12].
• Using PCR analyses of DNAs isolated from mouse x Chinese hamster somatic cell hybrids, we have mapped both the loricrin and the profilaggrin genes to chromosome 3 [13].
• The cornified cell envelope (CE) of terminally differentiating stratified squamous epithelial cells is a complex multiprotein assembly about 15 nm thick of which loricrin is a major component [11].
• Sulfur was found at high levels in round L-granules in the granulocyte cytoplasm and in the cornified CE, correlating with the presence of the protein, loricrin ( approximately 7% Cys/Met residues) [14].

Associations of Lor with chemical compounds

• Concurrently, there was diminished beta-glucocerebrosidase activity at the stratum granulosum-stratum corneum junction and a modest decrease in both involucrin and loricrin protein expression, markers of keratinocyte differentiation [15].
• Since loricrin is rich in cysteine, L-granules account for the sulfur-rich keratohyalin granules described earlier [16].
• To define the regulatory elements that mediate the expression of the loricrin gene, we replaced the loricrin coding sequences from a 6.5-kilobase genomic fragment with the chloramphenicol acetyltransferase gene and transfected this construct into cultured mouse keratinocytes [17].
• The induction of filaggrin and loricrin by CS corresponds to a granular layer differentiation program, where PKC activation occurs and was blocked by the PKC inhibitor GF 109203X [18].
• Isolation of a GC-rich cDNA identifying mRNA present in human epidermis and modulated by calcium and retinoic acid in cultured keratinocytes. Homology with murine loricrin mRNA [19].

Regulatory relationships of Lor

• Yin-yang 1 negatively regulates the differentiation-specific transcription of mouse loricrin gene in undifferentiated keratinocytes [9].

Other interactions of Lor

• The basal cells of affected mice ceased to proliferate, and expressed the profilaggrin and loricrin genes which are normally transcribed only in the latest stages of epidermal differentiation [20].
• These findings suggest that YY1 contributes to specific loricrin gene expression in differentiated keratinocytes by suppression of its transcription in undifferentiated keratinocytes [9].
• BAPTA also inhibited the expression of K1, K10 and loricrin mRNA [21].
• Cytokeratin 5 was localized in the lowest cell layer in the epithelial sheet, but cytokeratin 1 and loricrin were localized in the outer cell layers, resembling mouse skin [22].
• Furthermore, the expression of both mRNA and protein for the calcium inducible keratinocyte differentiation markers, filaggrin and loricrin, were down-regulated in the epidermis of Casr(-/-) mice, whereas the number of proliferating cells were increased even though the calcium gradient within the epidermis was enhanced [23].

Analytical, diagnostic and therapeutic context of Lor

• We refined mapping of the mouse gene and other markers on a radiation hybrid panel of Chr 3 and found the order cen, Acrb2, Lor, Iv1, Flg, tel [24].
• We have used immunoelectron microscopy to map the biosynthetic pathways of loricrin and filaggrin in epidermal keratinocytes at successive stages of differentiation in newborn mouse skin [16].
• Three hours after acute barrier disruption, coincident with reduced calcium and ultrastructural evidence of accelerated lamellar body secretion, both northern analyses and in situ hybridization revealed decreased mRNA levels for loricrin, profilaggrin, and involucrin in the outer epidermis, but protein levels did not change significantly [25].
• Epidermal differentiation marker proteins such as involucrin, loricrin, and keratin1 were also increased in PS-treated NHEKs, by ELISA or Western blotting analysis [26].
• At a later developmental time and after birth, expression of filaggrin and loricrin is indistinguishable between treatment and control groups [27].

References