University of Oulu

Kreus, M., Lehtonen, S., Hinttala, R. et al. NHLRC2 expression is increased in idiopathic pulmonary fibrosis. Respir Res 23, 206 (2022).

NHLRC2 expression is increased in idiopathic pulmonary fibrosis

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Author: Kreus, Mervi1,2; Lehtonen, Siri3,4; Hinttala, Reetta4,5;
Organizations: 1Research Unit of Internal Medicine, University of Oulu, Oulu, Finland
2Center of Internal Medicine and Respiratory Medicine and Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland
3Department of Obstetrics and Gynecology and Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland
4Medical Research Center Oulu and PEDEGO Research Unit, University of Oulu and Oulu University Hospital, Oulu, Finland
5Biocenter Oulu, University of Oulu, Oulu, Finland
6Department of Forensic Medicine, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.5 MB)
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Language: English
Published: Springer Nature, 2022
Publish Date: 2023-01-04


Background: Variants of NHL repeat-containing protein 2 (NHLRC2) have been associated with severe fibrotic interstitial lung disease in early childhood and NHLRC2 has been listed as a differentially expressed gene between rapidly and slowly progressing idiopathic pulmonary fibrosis (IPF) patients. However, its cell type-specific localization in human lung tissue is unknown. The aim of this study was to evaluate NHLRC2 mRNA and protein expression in different cell types of lung tissue samples and to investigate the effect of transforming growth factor (TGF)-β1 exposure on NHLRC2 expression in vitro.

Methods: The NHLRC2 expression in lung tissue samples was studied by immunohistochemistry (50 IPF, 10 controls) and mRNA in situ hybridization (8 IPF, 3 controls). The immunohistochemical NHLRC2 expression was quantified with image analysis software and associated with the clinical and smoking data of the patients. NHLRC2 expression levels in primary stromal and small airway epithelial cell lines after exposure to TGF-β1 was measured by quantitative reverse transcription polymerase chain reaction and Western blot analysis.

Results: NHLRC2 expression was detected especially in bronchiolar epithelial cells, type II pneumocytes and macrophages in normal lung. In the lungs of IPF patients, NHLRC2 was mainly expressed in hyperplastic alveolar epithelial cells lining fibroblast foci and honeycombs. NHLRC2 expression assessed by image analysis was higher in IPF compared to controls (p < 0.001). Ever-smokers had more prominent NHLRC2 staining than non-smokers (p = 0.037) among IPF patients. TGF-β1 exposure did not influence NHLRC2 levels in lung cell lines.

Conclusions: NHLRC2 expression was higher in IPF compared to controls being widely expressed in type II pneumocytes, macrophages, bronchiolar epithelium, and hyperplastic alveolar epithelium. Additionally, its expression was not regulated by the exposure to TGF-β1 in vitro. Further studies are needed to clarify the role of NHLRC2 in IPF.

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Series: Respiratory research
ISSN: 1465-9921
ISSN-E: 1465-9921
ISSN-L: 1465-9921
Volume: 23
Issue: 1
Article number: 206
DOI: 10.1186/s12931-022-02129-z
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This work was supported by the Tampere Tuberculosis foundation (MK), Väinö and Laina Kivi Foundation (MK), Orion research foundation (MK), University of Oulu Graduate School (virtual congress costs, MK), Foundation of the Finnish Anti-Tuberculosis Association (MK, JS, RK), the Research Foundation of the Pulmonary Diseases (MK, JS, RK), Medical Research Center (MRC) Oulu, Oulu University Hospital, Oulu, Finland (SL), Academy of Finland profiling program (grant #311934) (RH), the Foundation for Pediatric Research, Finland (RH), Jalmari and Rauha Ahokas Foundation (RK), the Research Foundation of North Finland, Oulu, Finland (RK), and a state subsidy of Oulu University Hospital (RK).
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