Biomaterial Database

TREM-1 exacerbates bleomycin-induced pulmonary fibrosis by aggravating alveolar epithelial cell senescence in mice. 2022

Jian-Bing Xiong, and Jia-Xi Duan, and Nan Jiang, and Chen-Yu Zhang, and Wen-Jing Zhong, and Jin-Tong Yang, and Yu-Biao Liu, and Feng Su, and Yong Zhou, and Dai Li, and Hui-Hui Yang, and Cha-Xiang Guan

Department of Emergency, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China; Department of Physiology, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China; National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.

Our previous study showed that triggering receptors expressed on myeloid cell-1 (TREM-1) was upregulated in bleomycin (BLM)-induced pulmonary fibrosis (PF) mouse model. However, the role of TREM-1 in the development of PF and its underlying mechanism remain unclear. Herein, we report that the prophylactical blockade of TREM-1 using a decoy peptide dodecapeptide (LR12) exerted protective effects against BLM-induced PF in mice, with a higher survival rate, attenuated tissue injury, and less extracellular matrix deposition. Interestingly, therapeutic blockade of TREM-1 at the early stage of fibrosis also attenuated BLM-induced PF, suggesting a non-inflammatory effect. More importantly, we observed that TREM-1 blockade with LR12 significantly reduced the expression of the senescence-relative protein, including p16, p21, p53, and γ-H2AX in the lungs of PF mice. Notably, TREM-1 was upregulated in alveolar epithelial cells (AECs) and correlated with the levels of senescence markers in BLM-treated mice. In vitro, activating TREM-1 with an agonistic antibody exacerbated BLM-induced senescence in MLE12 cells, a murine AEC cell line. Furthermore, prophylactic or therapeutic blockade of TREM-1 protected MLE12 cells from senescence induced by BLM or H2O2. In conclusion, our findings elucidate a pro-fibrotic effect of TREM-1 by inducing AECs senescence in PF, providing a potential strategy for fibrotic disease treatment.

UI	MeSH Term	Description	Entries
D011658	Pulmonary Fibrosis	A process in which normal lung tissues are progressively replaced by FIBROBLASTS and COLLAGEN causing an irreversible loss of the ability to transfer oxygen into the bloodstream via PULMONARY ALVEOLI. Patients show progressive DYSPNEA finally resulting in death.	Alveolitis, Fibrosing,Idiopathic Diffuse Interstitial Pulmonary Fibrosis,Fibroses, Pulmonary,Fibrosis, Pulmonary,Pulmonary Fibroses,Alveolitides, Fibrosing,Fibrosing Alveolitides,Fibrosing Alveolitis
D001761	Bleomycin	A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors.	BLEO-cell,Blanoxan,Blenoxane,Bleolem,Bleomicina,Bleomycin A(2),Bleomycin A2,Bleomycin B(2),Bleomycin B2,Bleomycin Sulfate,Bleomycins,Bleomycinum Mack,Bléomycine Bellon,BLEO cell,BLEOcell,Bellon, Bléomycine,Mack, Bleomycinum,Sulfate, Bleomycin
D006861	Hydrogen Peroxide	A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.	Hydrogen Peroxide (H2O2),Hydroperoxide,Oxydol,Perhydrol,Superoxol,Peroxide, Hydrogen
D000073871	Triggering Receptor Expressed on Myeloid Cells-1	An approximately 230 amino acid membrane glycoprotein characterized by an IMMUNOGLOBULIN V-SET DOMAIN in its N-terminal half. It is expressed by MONOCYTES and NEUTROPHILS in response to INFLAMMATION related to bacterial and fungal infections. It triggers the release of pro-inflammatory CHEMOKINES; CYTOKINES, and expression of cell activation markers and is a critical regulator of SEPTIC SHOCK.	CD354 Antigen,TREM-1 Protein,Antigen, CD354,TREM 1 Protein,Triggering Receptor Expressed on Myeloid Cells 1
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D056809	Alveolar Epithelial Cells	Epithelial cells that line the PULMONARY ALVEOLI.	Pneumocytes,Alveolar Cells,Pneumocyte,Type 1 Pneumocytes,Type 2 Pneumocytes,Type-I Pneumocytes,Type-II Pneumocytes,Alveolar Cell,Alveolar Epithelial Cell,Cell, Alveolar,Cell, Alveolar Epithelial,Cells, Alveolar,Cells, Alveolar Epithelial,Epithelial Cell, Alveolar,Epithelial Cells, Alveolar,Pneumocyte, Type 1,Pneumocyte, Type 2,Pneumocyte, Type-I,Pneumocyte, Type-II,Pneumocytes, Type 1,Pneumocytes, Type 2,Pneumocytes, Type-I,Pneumocytes, Type-II,Type 1 Pneumocyte,Type 2 Pneumocyte,Type I Pneumocytes,Type II Pneumocytes,Type-I Pneumocyte,Type-II Pneumocyte
D022423	Myeloid Cells	The classes of BONE MARROW-derived blood cells in the monocytic series (MONOCYTES and their precursors) and granulocytic series (GRANULOCYTES and their precursors).	Cell, Myeloid,Cells, Myeloid,Myeloid Cell