Journal article
Human placental mesenchymal stem cells of fetal origins-alleviated inflammation and fibrosis by attenuating MyD88 signaling in bleomycin-induced pulmonary fibrosis mice
Molecular immunology, Vol.90, pp.11-21
10/2017
DOI: 10.1016/j.molimm.2017.06.032
PMID: 28662409
Abstract
•The deficiency of MyD88 ameliorates bleomycin-induced pulmonary fibrosis in mice.•TGF-β1 inhibits MyD88 signaling in pulmonary cells.•Augmentation of MyD88 protein enhances TGF-β signaling in pulmonary cells.•Human placental MSCs of fetal origins can attenuate bleomycin-induced pulmonary inflammation and fibrosis in mice.•A crosstalk of TGF-β/MyD88 signaling may be important in maintaining the homeostasis and functional integrity of lung during injury.
Pulmonary fibrosis is a progressive lung disease that its pathogenic mechanism currently is incompletely understood. Toll-like receptor (TLR) signaling has recently been identified as a regulator of inflammation and pulmonary fibrosis. In addition, mesenchymal stem cells (MSCs) of different origins offer a great promise in treatment of idiopathic pulmonary fibrosis (IPF). However mechanisms of pathogenic roles of TLR signaling and therapeutic effects of MSCs in the IPF remain elusive. In present study, the involvement of TLR signaling and the therapeutic role of MSCs were interrogated in MyD88-deficient mice using human placental MSCs of fetal origins (hfPMSCs). The results showed an alleviated pulmonary inflammation and fibrosis in myeloid differentiation primary response gene 88 (MyD88)-deficient mice treated with bleomycin (BLM), accompanied with a reduced TGF-β signaling and production of pro-fibrotic cytokines, including TNF-α, IL-1β. An exposure of HLF1 lung fibroblasts, A549 epithelial cells and RAW264.7 macrophages to BLM led an increased expression of key components of MyD88 and TGF-β signaling cascades. Of interest, enforced expression and inhibition of MyD88 protein resulted in an enhanced and a reduced TGF-β signaling in above cells in the presence of BLM, respectively. However, the addition of TGF-β1 showed a marginally inhibitory effect on MyD88 signaling in these cells in the absence of BLM. Importantly, the administration of hfPMSCs could significantly attenuate BLM-induced pulmonary fibrosis in mice, along with a reduced hydroxyproline (HYP) deposition, MyD88 and TGF-β signaling activation, and production of pro-fibrotic cytokines. These results may suggest an importance of MyD88/TGF-β signaling axis in the tissue homeostasis and functional integrity of lung in response to injury, which may offer a novel target for treatment of pulmonary fibrosis.
Details
- Title: Subtitle
- Human placental mesenchymal stem cells of fetal origins-alleviated inflammation and fibrosis by attenuating MyD88 signaling in bleomycin-induced pulmonary fibrosis mice
- Creators
- Feng Li - Center of Laboratory Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaFei Han - Department of Laboratory Medicine, College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaHui Li - Department of Laboratory Medicine, College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaJia Zhang - Department of Laboratory Medicine, College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaXia Qiao - Center of Laboratory Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaJuan Shi - Center of Laboratory Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaLi Yang - The Center of Experimental Animals, Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaJianda Dong - Department of Pathology, Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaMeihui Luo - Center of Laboratory Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaJun Wei - Center of Laboratory Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaXiaoming Liu - College of Life Science, Ningxia University, Yinchuan, Ningxia 750021, China
- Resource Type
- Journal article
- Publication Details
- Molecular immunology, Vol.90, pp.11-21
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.molimm.2017.06.032
- PMID
- 28662409
- ISSN
- 0161-5890
- eISSN
- 1872-9142
- Grant note
- DOI: 10.13039/501100001809, name: National Natural Science Foundation of China, award: 31472191, 81460247; name: Natural Science Foundation of Ningxia Hui Autonomous Region of China, award: NZ14286
- Language
- English
- Date published
- 10/2017
- Academic Unit
- Anatomy and Cell Biology; Pathology
- Record Identifier
- 9984025370402771
Metrics
22 Record Views