C-kit+ Cells Offer Hopes in Ameliorating Asthmatic Pathologies Via Regulation of MiRNA-133 and MiRNA-126

Overview

Journal Iran J Basic Med Sci

Publisher Mashhad University of Medical Sciences

Specialty General Medicine

Date 2021 May 17

PMID 33995948

Citations 8

Authors

Reza Rahbarghazi

Rana Keyhanmanesh

Jafar Rezaie

Fatemeh Mirershadi

Hossain Heiran

Hesam Saghaei Bagheri

Shirin Saberianpour

Aysa Rezabakhsh

Aref Delkhosh

Yasin Bagheri

Hadi Rajabi

Mahdi Ahmadi

Affiliations

Soon will be listed here.

Abstract

Objectives: 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 (<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 (<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 (<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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