Sprr4 is a member of the small proline-rich proteins (SPRRs) family and serves as a novel cornified envelope (CE) precursor. The CE, formed in the outermost layers of stratified squamous epithelia, provides a physical barrier against environmental insults [1,5]. Sprr4 is involved in the process of epidermal differentiation and likely plays a role in maintaining the integrity of the skin barrier [1,2,4,6]. Genetic models, such as mouse models, can be valuable in further exploring its function.

In mice, the murine ortholog of SPRR4 was identified within the tandemly arrayed Sprr locus on chromosome 3. In a model of barrier deficiency (Klf4 -/- mice), 12 out of 15 members of the Sprr family were upregulated, though it's not clear if SPRR4 was among them [3]. In human studies, SPRR4 expression was very low or undetectable in normal skin but was induced by UV light, both in vivo and in vitro. After chronic UV exposure, high epidermal expression of SPRR4 was observed, accompanied by thickening of the stratum corneum, suggesting it compensates for UV-induced impairment of the epidermal barrier function. Interestingly, after UV irradiation, SPRR4 was selectively incorporated into fragile CEs [1]. In atopic dermatitis, SPRR4 had a significant decrease in expression in lesional versus non-lesional skin, which persisted after pimecrolimus treatment [4]. Also, isosorbide di-(linoleate/oleate) (IDL) effectively upregulated SPRR4 expression, increased the abundance of epidermal barrier proteins, and improved skin hydration [6].

In conclusion, Sprr4 is an important CE precursor involved in the adaptive tissue response to environmental stress, especially UV-induced damage, and is associated with maintaining skin barrier function. Studies in mouse models, along with human-based research, have provided insights into its role in conditions related to skin barrier dysfunction, such as UV-damaged skin and atopic dermatitis.

References:

1. Cabral, A, Sayin, A, de Winter, S, Pavel, S, Backendorf, C. . SPRR4, a novel cornified envelope precursor: UV-dependent epidermal expression and selective incorporation into fragile envelopes. In Journal of cell science, 114, 3837-43. doi:. https://pubmed.ncbi.nlm.nih.gov/11719550/

2. Jeriha, Jakob, Kolundzic, Nikola, Khurana, Preeti, Mauro, Theodora M, Ilic, Dusko. 2020. Markers for Ca++ -induced terminal differentiation of keratinocytes in vitro under defined conditions. In Experimental dermatology, 29, 1238-1242. doi:10.1111/exd.14199. https://pubmed.ncbi.nlm.nih.gov/32978827/

3. Patel, Satyakam, Kartasova, Tonja, Segre, Julia A. . Mouse Sprr locus: a tandem array of coordinately regulated genes. In Mammalian genome : official journal of the International Mammalian Genome Society, 14, 140-8. doi:. https://pubmed.ncbi.nlm.nih.gov/12584609/

4. Grzanka, Alicja, Zebracka-Gala, Jadwiga, Rachowska, Regina, Kowalska, Małgorzata, Jarzab, Jerzy. 2011. The effect of pimecrolimus on expression of genes associated with skin barrier dysfunction in atopic dermatitis skin lesions. In Experimental dermatology, 21, 184-8. doi:10.1111/j.1600-0625.2011.01417.x. https://pubmed.ncbi.nlm.nih.gov/22142393/

5. Cabral, A, Voskamp, P, Cleton-Jansen, A M, Nizetic, D, Backendorf, C. 2001. Structural organization and regulation of the small proline-rich family of cornified envelope precursors suggest a role in adaptive barrier function. In The Journal of biological chemistry, 276, 19231-7. doi:. https://pubmed.ncbi.nlm.nih.gov/11279051/

6. Bojanowski, Krzysztof, Swindell, William R, Cantor, Shyla, Chaudhuri, Ratan K. 2020. Isosorbide Di-(Linoleate/Oleate) Stimulates Prodifferentiation Gene Expression to Restore the Epidermal Barrier and Improve Skin Hydration. In The Journal of investigative dermatology, 141, 1416-1427.e12. doi:10.1016/j.jid.2020.09.029. https://pubmed.ncbi.nlm.nih.gov/33181142/