Abstract
Bone marrow mesenchymal stem cells (BMSCs) have multi-lineage differentiation potential and play an important role in tissue repair. Studies have shown that BMSCs gather at the injured tissue site after granulocyte-colony stimulating factor (G-CSF) administration. In this study, we first investigated whether G-CSF could promote BMSC homing to damaged lung tissue induced by bleomycin (BLM) and then investigated whether SDF-1/CXCR4 chemotaxis might be involved in this process. Next, we further studied the potential inhibitory effect of G-CSF administration in mice with lung fibrosis induced by bleomycin. We examined both the antifibrotic effects of G-CSF in mice with bleomycin-induced pulmonary fibrosis in vivo and its effects on the proliferation, differentiation and chemotactic movement of cells in vitro. Flow cytometry, real-time PCR, transwell and Cell Counting Kit-8 (CCK-8) assays were used in this study. The results showed that both preventative and therapeutic G-CSF administration could significantly inhibit bleomycin-induced pulmonary fibrosis. G-CSF enhanced BMSC migration to lung tissues, but this effect could be alleviated by AMD3100, which blocked the SDF-1/CXCR4 axis. We also found that BMSCs could inhibit fibroblast proliferation and transdifferentiation into myofibroblasts through paracrine actions. In conclusion, G-CSF exerted antifibrotic effects in bleomycin-induced lung fibrosis, in part by promoting BMSC homing to injured lung tissues via SDF-1/CXCR4 chemotaxis.
Highlights
Bone marrow mesenchymal stem cells (BMSCs) have multi-lineage differentiation potential and play an important role in tissue repair
Our results show that granulocyte-colony stimulating factor (G-CSF) exerts antifibrotic effects in bleomycin-induced lung fibrosis
After inducing Transforming growth factor-β (TGF-β), these two indicators were lower when using BMSC-conditioned medium than when using standard or FB-conditioned medium (Fig. 5B,C). These results indicated that BMSCs attenuated the proliferation and transdifferentiation of FBs through paracrine www.nature.com/scientificreports www.nature.com/scientificreports www.nature.com/scientificreports proliferation and transdifferentiation. (A) Cell proliferation was measured by Cell Counting Kit-8 (CCK-8) assay after culture with different media. (B) HYP content in the supernatant and (C) α-Smooth muscle actin (α-SMA) mRNA expression were quantified at 24 hours after various treatments. (D) Cell proliferation, HYP content and α-SMA mRNA expression were measured after culture with various media for 24 hours
Summary
Bone marrow mesenchymal stem cells (BMSCs) have multi-lineage differentiation potential and play an important role in tissue repair. We first investigated whether G-CSF could promote BMSC homing to damaged lung tissue induced by bleomycin (BLM) and investigated whether SDF-1/CXCR4 chemotaxis might be involved in this process. G-CSF exerted antifibrotic effects in bleomycin-induced lung fibrosis, in part by promoting BMSC homing to injured lung tissues via SDF-1/ CXCR4 chemotaxis. Developing effective methods for promoting autologous MSC participation in tissue repair has become an alternative approach in stem cell research and is of great significance for improving clinical treatments. Studies have found that SDF-1 and its specific receptor CXCR4 play an important role in stem cell mobilization, chemotaxis, homing and colonization of damaged myocardial tissue[11,12]. That up-regulation of the expression of CXCR4 on the surface of BMSCs promote more BMSCs to migrate to damaged tissues, and will be more conducive to tissue damage repair
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
