Abstract
Mutations of lamin genes lead to diseases, one of which is progeria. This disease is caused by violation of splicing of lamin A gene and accumulation of farnesylated prelamin A (progerin) in the nucleus. LAP-2 is an important factor that regulates and stabilizes the nucleoplasmic pool of lamin A. However, roles of lamin A and LAP-2 in renewal regulation of the population of fibroblasts in the human dermis in different age periods still have not been investigated. The purpose of this investigation was to define expression of lamin A and LAP-2 in human dermal fibroblasts at different ages. Lamin A and LAP-2 were detected in skin sections by indirect immunohistochemistry. It was found that the number of fibroblasts containing lamin A gradually decreased from 90.4 to 76.9% from 20 weeks of pregnancy to 85 years. It was revealed that 32% of dermal fibroblasts were positively stained for LAP-2 in the period from 20 weeks of pregnancy to 20 years, 37.8% in the period of 21–40 years, and 49–51% in the period of 41–85 years. Lamin A expression levels in fibroblast nuclei were essentially constant from 20 weeks of pregnancy to 85 years, while LAP-2 content in fibroblast nuclei was reducing from 0 to 20 years as compared with the embryonic period and was gradually increasing after 21 year. The total number of fibroblasts and PCNA-positive fibroblasts in the dermis decreased with age. The most significant decrease in the number of fibroblasts was observed from 20 weeks of pregnancy to 20 years. The results suggest involvement of lamin A and LAP-2 in the age-related decrease in the number of fibroblasts in the human dermis.
Similar content being viewed by others
References
Gunin, A.G., Osipova, A.A., Samoilova, A.V., et al., Role of NUMB in morphogenetic changes in the uterus affected by estrogens and glucocorticoids, Probl. Reproduktol., 2009, no. 3, pp. 15–20.
Barton, L.J., Soshnev, A.A., and Geyer, P.K., Networking in the nucleus: a spotlight on LEM-domain proteins, Curr. Opin. Cell Biol., 2015, vol. 34, pp. 1–8.
Brachner, A. and Foisner, R., Lamina-associated polypeptide LAP-2 and other LEM proteins in cancer biology, Adv. Exp. Med. Biol., 2014, vol. 773, pp. 143–163.
Braidy, N., Poljak, A., Grant, R., et al., Differential expression of sirtuins in the aging rat brain, Front. Cell Neurosci., 2015, vol. 9, p. 167.
Cao, K., Blair, C.D., Faddah, D.A., et al., Progerin and telomere dysfunction collaborate to trigger cellular senescence in normal human fibroblasts, J. Clin. Invest., 2011, vol. 121, no. 7, pp. 2833–2844.
Gesson, K., Vidak, S., and Foisner, R., Lamina-associated polypeptide (LAP)2 and nucleoplasmic lamins in adult stem cell regulation and disease, Semin. Cell Dev. Biol., 2014, vol. 29, pp. 116–124.
Gordon, L.B., Kleinman, M.E., Miller, D.T., et al., Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson–Gilford progeria syndrome, Proc. Natl. Acad. Sci. U.S.A., 2012, vol. 109, no. 41, pp. 16666–16671.
Gunin, A.G., Kornilova, N.K., Vasilieva, O.V., et al., Age-related changes in proliferation, the numbers of mast cells, eosinophils, CD45 positive cells in human dermis, J. Gerontol., Ser. A, 2011, vol. 66, no. 4, pp. 385–392.
Gunin, A.G., Petrov, V.V., Golubtzova, N.N., et al., Age-related changes in angiogenesis in human dermis, Exp. Gerontol., 2014, vol. 55, pp. 143–151.
Hutchison, C.J., B-type lamins in health and disease, Semin. Cell Dev. Biol., 2014, vol. 29, pp. 158–163.
Lund, E. and Collas, P., Nuclear laminas: making contacts with promoters, Nucleus, 2013, vol. 4, no. 6, pp. 424–430.
McClintock, D.I., Ratner, D., Lokuge, M., et al., The mutant form of lamin A that causes Hutchinson-Gilford progeria is a biomarker of cellular aging in human skin, PLoS One, 2007, vol. 2, no. 12, p. e1269.
McKenna, T., Rosengardten, Y., Viceconte, N., et al., Embryonic expression of the common progeroid lamin A splice mutation arrests postnatal skin development, Aging Cell, 2014, vol. 13, no. 2, pp. 292–302.
Rinnerthaler, M., Bischof, J., Streubel, M.K., et al., Oxidative stress in aging human skin, Biomolecules, 2015, vol. 5, no. 2, pp. 545–589.
Skoczyńska, A., Budzisz, E., Dana, A., et al., New look at the role of progerin in skin aging, Przegl. Menopauzalny, 2015, vol. 14, no. 1, pp. 53–58.
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © N.N. Golubtsova, F.N. Filippov, A.G. Gunin, 2016, published in Uspekhi Gerontologii, 2016, Vol. 29, No. 4, pp. 577–585.
Rights and permissions
About this article
Cite this article
Golubtsova, N.N., Filippov, F.N. & Gunin, A.G. Lamin A and lamin-associated polypeptide 2 (LAP-2) in human skin fibroblasts in the process of aging. Adv Gerontol 7, 60–67 (2017). https://doi.org/10.1134/S2079057017010076
Published:
Issue Date:
DOI: https://doi.org/10.1134/S2079057017010076