title: The apelin-APJ axis: A novel potential therapeutic target for organ fibrosis.
abstract: Apelin, an endogenous ligand of the G-protein-coupled receptor APJ, is expressed in a diverse number of organs. The apelin-APJ axis helps to control the processes of pathological and physiological fibrosis, including renal fibrosis, cardiac fibrosis, liver fibrosis and pulmonary fibrosis. However, the role of apelin-APJ in organ fibrosis remains controversial due to conflicting study results. The apelin-APJ axis is a detrimental mechanism which promotes liver fibrosis mainly via up-regulation the expression of collagen-II and platelet-derived growth factor receptor β (PDGFRβ). On the contrary, the apelin-APJ axis is beneficial for renal fibrosis, cardiac fibrosis and pulmonary fibrosis. The apelin-APJ axis alleviates renal fibrosis by restraining the expression of transforming growth factor-β1 (TGF-β1). In addition, the apelin-APJ axis attenuates cardiac fibrosis through multiple pathways. Furthermore, the apelin-APJ axis has beneficial effects on experimental bronchopulmonary dysplasia (BPD) and acute respiratory distress syndrome (ARDS) which suggest the apelin-APJ axis potentially alleviates pulmonary fibrosis. In this article, we review the controversies associated with apelin-APJ in organ fibrosis and introduce the drugs that target apelin-APJ. We conclude that future studies should place more emphasis on the relationship among apelin isoforms, APJ receptor subtypes and organ fibrosis. The apelin-APJ axis will be a potential therapeutic target and those drugs targeted for apelin-APJ may constitute a novel therapeutic strategy for renal fibrosis, cardiac fibrosis, liver fibrosis and pulmonary fibrosis.
authors.affiliation: Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang 421001, China.
authors.forename: Shifang
authors.initials: S
authors.lastname: Huang
authors.affiliation: Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang 421001, China.
authors.forename: Linxi
authors.initials: L
authors.lastname: Chen
authors.affiliation: Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang 421001, China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Lu
authors.affiliation: Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang 421001, China. Electronic address: llanfang6@126.com.
authors.forename: Lanfang
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D005355:Fibrosis / Q000188:drug therapy*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D058990:Molecular Targeted Therapy / Q000379:methods*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled
keywords: Apelin–APJ; Cardiac fibrosis; Liver fibrosis; Pulmonary fibrosis; Renal fibrosis