Specific microRNA signatures responsible for immune disturbance related to hip fracture in aged rats

Xiaobin Chen,Tiansheng Sun,Simeng Zhang,Zhi Liu,Jianzheng Zhang

doi:10.1186/s13018-018-0721-5

Abstract

BackgroundHip fracture is commonly associated with an overwhelming inflammatory response, which may lead to high rates of morbidity and mortality in the elderly. MicroRNAs (miRNAs) play important roles in the functions of immune system. However, the association between miRNA dysregulation and immune disturbance (IMD) related to elderly hip fracture is largely unknown.MethodsIn this study, microarray profiling was carried out to evaluate the differential expression patterns of miRNAs in plasma of the aged hip fracture rats with IMD, those without IMD, and normal aged rats, followed by validation using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Genes and signaling pathways of the dysregulated miRNAs related to elderly hip fracture-induced IMD were investigated in silico using Gene Ontology and analysis of Kyoto Encyclopedia of Genes or Genomes.ResultsDead or moribund rats with hip fracture exhibited significantly reduced TNF-α/IL-10 ratio compared with healthy controls and other hip fracture rats, which were therefore named as hip fracture rats with IMD. Seven serum miRNAs in hip fracture rats with IMD were significantly downregulated. qRT-PCR and in silico analysis revealed that miR-130a-3p likely participated in regulating the hip fracture-induced IMD. Furthermore, Western blot experiment demonstrated that in lung tissue, the reduction of miR-130a-3p was accompanied with the increase of the protein expression of interferon regulatory factor-1 (IRF1) and sphingosine-1-phosphate receptor 1 (SIPR1).ConclusionsmiR-130a-3p desregulation may be associated with elderly hip fracture-induced IMD, which might act as a new potential biomarker for the diagnosis and prognosis of elderly hip fracture-induced IMD and a potential therapeutic target as well.

Highlights

Hip fracture is commonly associated with an overwhelming inflammatory response, which may lead to high rates of morbidity and mortality in the elderly
The serum levels of both tumor necrosis factor-α (TNF-α) and IL-10 in hip fracture rats were gradually decreased after the operation, and the levels at 24, 48, or 72 h except that of serum IL-10 at 72 h were significantly higher than in normal rats (P < 0.01, Fig. 1a, b). 13.3% (6 of 45) of hip fracture rats were dead or became moribund at 72 h after hip fracture, and simultaneously, the serum TNF-α/IL-10 ratio in these rats was significantly downregulated compared with that in normal rats and other hip fracture rats (Fig. 1c)
Validation of the differentially expressed miRNAs by quantitative real-time reverse transcription polymerase chain reaction (qRTPCR) To validate the reliability of the microarray result, 4 of the 13 differentially expressed miRNAs were selected for validation by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in the lung and serum of normal, immune disturbance (IMD), and non-IMD rats

Summary

Introduction

Hip fracture is commonly associated with an overwhelming inflammatory response, which may lead to high rates of morbidity and mortality in the elderly. MicroRNAs (miRNAs) play important roles in the functions of immune system. The association between miRNA dysregulation and immune disturbance (IMD) related to elderly hip fracture is largely unknown. Hip fracture remains a leading cause of excessive morbidity and mortality among old people [1, 2]. Mortality associated with hip fracture is over 20% within 6 months [2]. It has been shown that some microRNAs (miRNAs) (e.g., miR-155, miR-146, miR150) control the development and responses of the immune system [14]. There is little understanding on which miRNAs participate in the immune disturbance (IMD) related to hip fracture. This study might provide a new potential biomarker for the diagnosis and prognosis of IMD related to hip fracture in aged patients and a potential therapeutic target as well

Methods

Results

Discussion

Conclusion