Molecular and Cellular Biochemistry

, Volume 436, Issue 1–2, pp 189–199 | Cite as

Splicing factors differentially expressed in psoriasis alter mRNA maturation of disease-associated EDA+ fibronectin

  • E. Szlavicz
  • K. Szabo
  • G. Groma
  • Z. Bata-Csorgo
  • F. Pagani
  • L. Kemeny
  • M. Szell
Article

Abstract

The EDA+ fibronectin splicing variant is overexpressed in psoriatic non-lesional epidermis and sensitizes keratinocytes to mitogenic signals. However, regulation of its abundance is only partially understood. In our recent cDNA microarray experiment, we identified three SR-rich splicing factors—splicing factor, arginine/serine-rich 18 (SFRS18), peptidyl-prolyl cistrans isomerase G (PPIG), and luc-7 like protein 3 (LUC7L3)—which might be implicated in the preactivated states of keratinocytes in psoriatic non-involved skin and could also contribute to the regulation of fibronectin mRNA maturation. In this study, we investigated the role of LUC7L3, PPIG, and SFRS18 in psoriasis and in the mRNA maturation process of fibronectin. Regarding tissue staining experiments, we were able to demonstrate a characteristic distribution of the splicing factors in healthy, psoriatic non-involved and involved epidermis. Moreover, the expression profiles of these SR-rich proteins were found to be very similar in synchronized keratinocytes. Contribution of splicing facwwtors to the EDA+ fibronectin formation was also confirmed: their siRNA silencing leads to altered fibronectin mRNA and protein expression patterns, suggesting the participation in the EDA domain inclusion. Our results indicate that LUC7L3, PPIG, and SFRS18 are not only implicated in EDA+ fibronectin formation, but also that they could possess multiple roles in psoriasis-associated molecular abnormalities.

Keywords

Psoriasis mRNA splicing EDA+ fibronectin SR-rich splicing factors 

Notes

Acknowledgements

The study was supported by OTKA K105985, OTKA K111885 and TÁMOP-4.2.2.A-11/1/KONV-2012-0035, GINOP-2.3.2-15-2016-00015 research Grants.

Supplementary material

11010_2017_3090_MOESM1_ESM.tif (635 kb)
Supplementary material Fig. 1 Detection of LUC7L3, PPIG and SFRS18 mRNA expression in synchronized HaCaT cells. Cultures of HaCaT cells (n = 1) were synchronized by contact inhibition and serum withdrawal, and samples were collected at the indicated time points after re-passaging (0 h). The mRNA expression of the three splicing factors exhibits very similar expression patterns after release from cell quiescence (TIFF 634 kb)
11010_2017_3090_MOESM2_ESM.tif (1.6 mb)
Supplementary material Fig. 2 Efficacies of splicing factor silencing for different experimental setups. For each splicing regulator, values are the means of three independent experiments performed in triplicate (TIFF 1678 kb)

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of Dermatology and Allergology, Faculty of MedicineUniversity of SzegedSzegedHungary
  2. 2.MTA-SZTE Dermatological Research GroupSzegedHungary
  3. 3.Department of Medical Genetics, Faculty of MedicineUniversity of SzegedSzegedHungary
  4. 4.International Centre for Genetic Engineering and BiotechnologyTriesteItaly

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