TMEM45A Is Dispensable for Epidermal Morphogenesis, Keratinization and Barrier Formation

Abstract

TMEM45A gene encodes an initially uncharacterized predicted transmembrane protein. We previously showed that this gene is highly expressed in keratinocytes where its expression correlates with keratinization, suggesting a role in normal epidermal physiology. To test this hypothesis, we generated TMEM45A knockout mice and found that these mice develop without any evident phenotype. The morphology of the epidermis assessed by histology and by labelling differentiation markers in immunofluorescence was not altered. Toluidine blue permeability assay showed that the epidermal barrier develops normally during embryonic development. We also showed that depletion of TMEM45A in human keratinocytes does not alter their potential to form in vitro 3D-reconstructed epidermis. Indeed, epidermis with normal morphogenesis were generated from TMEM45A-silenced keratinocytes. Their expression of differentiation markers quantified by RT-qPCR and evidenced by immunofluorescence labelling as well as their barrier function estimated by Lucifer yellow permeability were similar to the control epidermis. In summary, TMEM45A gene expression is dispensable for epidermal morphogenesis, keratinization and barrier formation. If this protein plays a role in the epidermis, its experimental depletion can possibly be compensated by other proteins in the two experimental models analyzed in this study.

Analysis of the Single-Cell Heterogeneity of Adenocarcinoma Cell Lines and the Investigation of Intratumor Heterogeneity Reveals the Expression of Transmembrane Protein 45A (TMEM45A) in Lung Adenocarcinoma Cancer Patients

“…Lastly, Flamant et al described the expression of TMEM45A mRNA in hypoxic MDA-MB-231 human breast cancer cells and in HepG2 human hepatoma cells [ 44 ]. Hayez was the first to show the increase in the amount of TMEM45A protein close to the Golgi apparatus under hypoxic condition in murine embryonic fibroblasts [ 68 ]. In our IHC results, the expression of TMEM45A protein in lung adenocarcinoma was not exclusively reliant on HIF-α induction.…”

A case study investigating the short‐term efficacy and tolerability of a daily serum composed from a unique sunflower sprout extract

“…Meeting this criterion, 29 genes were found upregulated, and 116 genes were found downregulated. The pattern of upregulated genes corresponded to genes involved in epidermal differentiation, anti‐microbial peptide formation, epidermal barrier, and keratinization, which parallel the mechanism of action of the identified secondary metabolites found in the SSE 17–20 : LCE1B (fold change: 2.07; *** p < 0.001) KRT2 (fold change: 2.12; *** p < 0.001) TMEM45 (fold change: 2.22; *** p < 0.001) GABRB3 (fold change: 2.26; *** p < 0.001) LIPN (fold change: 3.23; *** p < 0.001) DEFB4a (fold change:3.16; * p < 0.05) …”

“…genes were found downregulated. The pattern of upregulated genes corresponded to genes involved in epidermal differentiation, antimicrobial peptide formation, epidermal barrier, and keratinization, which parallel the mechanism of action of the identified secondary metabolites found in the SSE [17][18][19][20] :…”

Homeobox transcription factor DLX4 is not necessary for skin development and homeostasis

“…Dlx4 KO mice were phenotypically indistinguishable from wild‐type counterparts, and skin transcriptome analysis did not determine any significant differentially expressed genes linked to the Dlx4 deletion. Indeed, there are mouse lines with knockouts for genes such as Calm4, periplakin, desmoyokin and TMEM45A, which are highly expressed in skin and yet present no overt skin phenotype . Lack of major phenotypic changes in Dlx4 KO mice suggests a non‐essential function in skin development and homeostasis, although its role in more challenging conditions such as exposure to UV‐B, injury or microbial infection remains to be determined.…”