PIN1‑silencing mitigates keratinocyte proliferation and the inflammatory response in psoriasis by activating mitochondrial autophagy.

Abstract

Peptidyl-prolyl cis/trans isomerase, NIMA-interacting 1 (PIN1) has been suggested to be a critical regulator in skin-related diseases. However, the role and molecular mechanism of PIN1 in psoriasis remain unclear. HaCaT cells were stimulated with five cytokines (M5) to induce psoriatic inflammation-like conditions. Reverse transcription-quantitative PCR and western blotting were performed to examine PIN1 expression in M5-induced HaCaT cells. A Cell Counting Kit-8 assay and 5-ethynyl-2'-deoxyuridine staining were employed to examine cell proliferation. Inflammatory factors were evaluated using ELISA kits and western blot analysis. Mitochondrial autophagy was examined by immunofluorescence staining, western blotting and a JC-1 assay. Western blot analysis was adopted to assess the levels of psoriasis marker proteins. PIN1 expression was markedly elevated in M5-induced HaCaT cells. Silencing of PIN1 inhibited M5-induced hyperproliferation and the inflammatory response, while it promoted mitochondrial autophagy in HaCaT cells. The addition of the mitochondrial autophagy inhibitor mitochondrial division inhibitor-1 reversed the effects of PIN1 interference on proliferation, the inflammatory response and mitochondrial autophagy in M5-induced HaCaT cells. The present study revealed that PIN1 inhibition protected HaCaT cells against M5-induced hyperproliferation and inflammatory injury through the activation of mitochondrial autophagy.