PRPF19 modulates morphology and growth behavior in a cell culture model of human skin

Lisa Kleissl; Regina Weinmüllner; Ingo Lämmermann; Ruth Dingelmaier-Hovorka; Mohammad Jafarmadar; Abdoelwaheb El Ghalbzouri; Georg Stary; Johannes Grillari; Hanna Dellago

doi:10.3389/fragi.2023.1154005

PRPF19 modulates morphology and growth behavior in a cell culture model of human skin

Front Aging. 2023 May 5:4:1154005. doi: 10.3389/fragi.2023.1154005. eCollection 2023.

Authors

Lisa Kleissl^{1

2

3}, Regina Weinmüllner^{4

5}, Ingo Lämmermann^{4

5}, Ruth Dingelmaier-Hovorka², Mohammad Jafarmadar⁶, Abdoelwaheb El Ghalbzouri⁷, Georg Stary^{1

2

3}, Johannes Grillari^{6

4}, Hanna Dellago^{4

5}

Affiliations

¹ Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria.
² Department of Dermatology, Medical University of Vienna, Vienna, Austria.
³ CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
⁴ Institute of Molecular Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria.
⁵ Christian Doppler Laboratory for Biotechnology of Skin Aging, Vienna, Austria.
⁶ Ludwig Boltzmann Institute for Traumatology in cooperation with AUVA, Vienna, Austria.
⁷ Department of Dermatology, Leiden University Medical Center, Leiden, Netherlands.

Abstract

The skin provides one of the most visual aging transformations in humans, and premature aging as a consequence of oxidative stress and DNA damage is a frequently seen effect. Cells of the human skin are continuously exposed to endogenous and exogenous DNA damaging factors, which can cause DNA damage in all phases of the cell cycle. Increased levels of DNA damage and/or defective DNA repair can, therefore, accelerate the aging process and/or lead to age-related diseases like cancer. It is not yet clear if enhanced activity of DNA repair factors could increase the life or health span of human skin cells. In previous studies, we identified and characterized the human senescence evasion factor (SNEV)/pre-mRNA-processing factor (PRPF) 19 as a multitalented protein involved in mRNA splicing, DNA repair pathways and lifespan regulation. Here, we show that overexpression of PRPF19 in human dermal fibroblasts leads to a morphological change, reminiscent of juvenile, papillary fibroblasts, despite simultaneous expression of senescence markers. Moreover, conditioned media of this subpopulation showed a positive effect on keratinocyte repopulation of wounded areas. Taken together, these findings indicate that PRPF19 promotes cell viability and slows down the aging process in human skin.

Keywords: DNA damage repair; DNA repair factor; PRPF19; SNEV; aging; fibroblast; wound healing.

Grants and funding

This work was funded by the Christian Doppler Research Association. The financial support by the Austrian Federal Ministry of Economy, Family, and Youth, the National Foundation for Research, Technology, and Development is also gratefully acknowledged, as is funding by the Herzfelder’sche Familienstiftung P35268B to JG.