Transcription Factor YY1 Inhibits the Expression of THY1 to Promote Interstitial Pulmonary Fibrosis by Activating the HSF1/miR-214 Axis

Abstract

Background: Pulmonary fibrosis is an inflammatory disease of pulmonary interstitium caused by many reasons. Recent studies have reported aberrant expression of microRNAs (miRNAs) in human embryonic pulmonary fibroblasts (HEPF), but their underlying mechanism remains to be further explored. In this study, we explored effect of YY1/HSF1/miR-214/THY1 axis on interstitial pulmonary fibrosis (IPF). Methods: IPF related microarray GSE24206 was downloaded from GEO database. Loss and gain of function tests were conducted to identify roles of YY1, HSF1, miR-214 and THY1 in IPF. The related expression of related indexes in tissues or cells was measured by qRT-PCR or western blot assay. Cell survival rate was detected by CCK8. Binding relationship between miR-214 and THY1 was verified using dual-luciferase reporter assay. Subsequently, IPF model in mice was induced by bleomycin. And the pathological changes of the lung tissues were assessed by HE and Masson staining, while the amount of collagen in the lung tissues of mice was measured by hydroxyproline assay. Results: In HEPF, YY1 promoted HSF1 and miR-214 expression, while miR-214 could promote the transformation HEPF by downregulating THY1. Silencing YY1 or HSF1 could inhibit the proliferation of HEPF and the expression of Ki67 and biomarkers of fibrosis, while overexpression of HSF1 or miR-214 could reverse this effect. Conclusion: Our study demonstrated the facilitating role of YY1/HSF1/miR-214/THY1 axis in the transformation of IPF. Funding Statement: The authors stated: None. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: Animals were treated humanely using approved procedures in compliance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Institutional Animal Care and Use Committee of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China.