RNA interference targeting interstitial collagenase is a potential therapeutic tool to treat psoriasis

Mogulevtseva YuA1, Mezentsev AV2, Bruskin SA2
About authors

1 Russian State Agrarian University – Timiryazev Moscow Agricultural Academy, Moscow, Russia

2 Laboratory of Functional Genomics, Department of Genetics and Biotechnology,
Vavilov Institute of General Genetics of the Russian Academy of Sciences, Moscow, Russia

Correspondence should be addressed: Aleksandr Mezentsev
ul. Gubkina, d. 3, Moscow, Russia, 119333; ur.ggiv@vestnesem

About paper

Acknowledgements: the authors thank Prof. Eleonora Piruzian of Vavilov Institute of General Genetics for a critical analysis of the manuscript and Prof. Maria Lagarkova of Vavilov Institute of General Genetics for the plasmids used in this study.

Contribution of all authors in data collection, analysis and interpretation was equal. Mogulevtseva AYu prepared all illustartions and Mezentsev AV drafted a manuscript. All authors participated in editing of the manuscript.

Received: 2017-02-17 Accepted: 2017-03-25 Published online: 2017-07-19

Matrix metalloproteinases play an important role in maintaining skin homeostasis, promote wound healing, and are involved in triggering inflammation. They are implicated in the structural changes occurring in the epidermis of psoriatic patients and also facilitate infiltration of the skin by immune cells by regulating permeability of dermal capillaries. In this light, control over the enzymatic activity of matrix metalloproteinases is crucial for a successful treatment outcome in patients with psoriasis. The aim of this work was to investigate the effect of RNA interference on the progression of psoriasis by targeting interstitial collagenase of epidermal keratinocytes. As part of the experiment, the latter were transduced with lentiviral particles that encode small hairpin RNA. Gene expression was measured by real time polymerase chain reaction. Enzymatic activity was measured by zymography. RNA interference was found to lead to a 20- and 4-fold decrease in the expression and enzymatic activity of interstitial collagenase, respectively. Expression of homologous genes (MMP2, -9 and -12) changed insignificantly. In contrast, there were marked changes in expression of cytokeratin (KRT1: 16.89 ± 0.97; KRT14: 2.36 ± 0.19; KRT17: 0.12 ± 0.01; KRT18: 0.56 ± 0.02), involucrin (0.79 ± 0.11) and filaggrin (6.99 ± 0.97). Besides, RNA interference caused a significant decline in cell migration rates, although it did not affect cell proliferation. Thus, small hairpin RNAs targeting interstitial collagenase are potentially therapeutic for psoriatic patients due to their ability to regulate expression of genes implicated in psoriasis (IVL, FLG, KRT1, -14 -17, and -18).

Keywords: psoriasis, interstitial collagenase, lentiviruses, transduction, transfection, small hairpin RNA, cytokeratins, involucrin, filaggrin