c-kit+ cells offer hopes in ameliorating asthmatic pathologies via regulation of miRNA-133 and -126
نویسندگان
1 Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
2 Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
3 Vascular and Endovascular Surgery Research Center, Mashhad University of Medical Science, Mashhad, Iran
4 Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
5 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
6 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
7 . Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
8 Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
9 Solid Tumor Research Center, Research Institute for Cellular and Molecular Medicine, Urmia University of Medical Sciences, Urmia, Iran
10 Department of Physiology, Ardabil Branch, Islamic Azad University, Ardabil, Iran
11 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
12 Young Researchers and Elite Club, Tabriz Branch Islamic Azad university, Tabriz, Iran
doi
10.22038/ijbms.2021.49008.11231چکیده
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.
