c-kit+ cells offer hopes in ameliorating asthmatic pathologies via regulation of miRNA-133 and -126

Document Type : Original Article


1 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

2 Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

3 Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

4 Solid Tumor Research Center, Research Institute for Cellular and Molecular Medicine, Urmia University of Medical Sciences, Urmia, Iran

5 Department of Physiology, Ardabil Branch, Islamic Azad University, Ardabil, Iran

6 Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

7 Vascular and Endovascular Surgery Research Center, Mashhad University of Medical Science, Mashhad, Iran

8 Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran

9 Young Researchers and Elite Club, Tabriz Branch Islamic Azad university, Tabriz, Iran


Objective(s): There are still challenges regarding c-kit+ cells’ therapeutic outcome in the clinical setting. Here, we examined the c-kit+ cell effect on the alleviation of asthma by modulating miRNAs expression.
Materials and Methods: To induce asthma, male rats were exposed to ovalbumin. Bone marrow-derived c-kit+ cells were enriched by MACS. Animals were classified into four groups (6 rats each). Control rats received PBS intratracheally; Ovalbumin-sensitized rats received PBS intratracheally; Ovalbumin-sensitized rats received PBS intratracheally containing 3×105 c-kit+ and c-kit- cells. Cells were stained with Dil fluorescent dye to track in vivo condition. Pathological changes were monitored in asthmatic rats after transplantation of c-kit+ and c-kit- cells. Serum levels of IL-4 and INF-γ were measured by ELISA. Transcription of miRNAs (-126 and 133) was assessed by real-time PCR analysis.
Results: Pathological examination and Th1 and Th2 associated cytokine fluctuation confirmed the occurrence of asthma in rats indicated by chronic changes and prominent inflammation compared with the control group (p <0.05). Both c-kit+ and c-kit- cells were verified in pulmonary niche. Administration of c-kit positive cells had the potential to change INF-γ/IL-4 ratio close to the normal values compared with matched-control asthmatic rats (p <0.05). We also found that c-kit+ cells regulated the expression of miRNA-126 and -133, indicated by an increase of miRNA-133 and decrease of miRNA-126 compared with cell-free sensitized groups (p <0.05).
Conclusion: c-kit- cells were unable to promote any therapeutic outcomes in the asthmatic milieu. c-kit+ cells had the potential to diminish asthma-related pathologies presumably by controlling the transcription of miRNA-126 and -133.


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