The apelin–APJ axis: A novel potential therapeutic target for organ fibrosis

Luo

Liu

et al. 2018

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Apelin is an endogenous ligand of seven‐transmembrane G‐protein‐coupled receptor APJ. Apelin and APJ are distributed in various tissues, including the heart, lung, liver, kidney, and gastrointestinal tract and even in tumor tissues. Studies show that apelin messenger RNA is widely expressed in gastrointestinal (GI) tissues, including stomach and small intestine, which is closely correlated with GI function. Thus, the apelin/APJ system may exert a broad range of activities in the digestive system. In this paper, we review the role of the apelin/APJ system in the digestive system in physiological conditions, such as gastric acid secretion, control of appetite and food intake, cell proliferation, cholecystokinin secretion and histamine release, gut–brain axis, GI motility, and others. In pathological conditions, the apelin/APJ system plays an important role in the healing process of stress gastric injury, the clinical features and prognosis of patients with gastric cancers, the reduction of inflammatory response to enteritis and pancreatitis, the mediation of liver fibrogenesis, the promotion of liver damage, the inhibition of liver regeneration, the contribution of splanchnic neovascularization in portal hypertension, the treatment of colon cancer, and GI oxidative damage. Overall, the apelin/APJ system plays diversified functions and regulatory roles in digestive physiology and pathology. Further exploration of the relationship between the apelin/APJ system and the digestive system will help to find new and effective drugs for treating and alleviating the pain of digestive diseases.

Section: The Role Of Apelin/apj System In Digestive System Diseasesmentioning

confidence: 99%

Section: The Potential Therapeutic Target Of Apelin/apj In Digestivmentioning

confidence: 99%

Function and regulation of apelin/APJ system in digestive physiology and pathology

Luo

Liu

et al. 2018

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“…A primary calcium mobilization assay and a secondary radioligand binding assay and focused screening A drug-like small molecule agonist Narayanan et al (2016) 2008), apelin-12 C3 (Hamada et al, 2008), and apelin-12 C4 (S. Huang et al, 2016). Maguire et al (2009) tested the hypothesis that apelins have vascular and cardiac actions in human tissues in vitro and compared responses with [Pyr1]apelin-13, apelin-13, and apelin-36 for the first time.…”

Section: Compound 22 C29h32n3o5fmentioning

confidence: 99%

Targeting drugs to APJ receptor: From signaling to pathophysiological effects

Chen

et al. 2018

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G-protein-coupled receptors (GPCRs) are recognized as the largest protein receptor superfamily, which are widely distributed in various tissues and organs. In addition, GPCRs are involved in many physiological and pathological longitudinal responses. Studies have indicated that putative receptor protein related to AT1 (APJ receptor) is an orphan GPCRs until its endogenous ligand apelin is found. Recently, Elabela, a new APJ receptor endogenous ligand was also found. Some evidence showed that the APJ receptor is distributed in the central nervous and cardiovascular systems. Moreover, the APJ receptor and its ligand are involved in many physiological functions and pathophysiological effects, making it a promising drug target for future treatment of diseases such as ischemic heart disease, hypertension, heart failure, and others. Although APJ is closely associated with many diseases, there are no drugs that can activate or inhibit APJ directly. In the current review, we try our best to summarize all agonists and antagonists targeting APJ, including peptides and small molecules. Given the role of apelin/APJ and Elabela/APJ in cardiovascular and other diseases, we believe that the combination of these agonists and antagonists with apelin and Elabela will play a corresponding role in various pathophysiological effects with further development of research.

“…Studies indicate that the level of apelin is elevated when mice are subject to UUO surgery and then treat with subsequent losartan treatment. Furthermore, losartan alleviates UUO-induced renal fibrosis via the apelin/APJ/Akt/eNOS pathway (Huang, Chen, Lu, & Li, 2016a). And apelin/APJ system can activate the endothelial nitric oxide synthase (eNOS) pathway (Ashley, Chun, & Quertermous, 2006;Huang et al, 2016a).…”

Section: Apelin/apj System Attenuates Renal Fibrosismentioning

confidence: 99%

“…Furthermore, losartan alleviates UUO-induced renal fibrosis via the apelin/APJ/Akt/eNOS pathway (Huang, Chen, Lu, & Li, 2016a). And apelin/APJ system can activate the endothelial nitric oxide synthase (eNOS) pathway (Ashley, Chun, & Quertermous, 2006;Huang et al, 2016a). Apelin/APJ system, interacting with losartan exerts a synergistic effect in attenuating renal fibrosis (Nishida et al, 2012).…”

Section: Apelin/apj System Attenuates Renal Fibrosismentioning

confidence: 99%

Apelin/APJ system: A novel potential therapy target for kidney disease

Chen

2017

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Apelin is an endogenous ligand of seven-transmembrane G protein-coupled receptor APJ. Apelin and APJ are distributed in various tissues, including the heart, lung, kidney, and even in tumor tissues. Studies show that apelin mRNA is highly expressed in the inner stripe of kidney outer medulla, which plays an important role in process of water and sodium balance. Additionally, more studies also indicate that apelin/APJ system exerts a broad range of activities in kidney. Therefore, we review the role of apelin/APJ system in kidney diseases such as renal fibrosis, renal ischemia/reperfusion injury, diabetic nephropathy, polycystic kidney disease, and hemodialysis (HD). Apelin/APJ system can improve renal interstitial fibrosis by reducing the deposition of extracellular matrix. Apelin/APJ system significantly reduces renal ischemia/reperfusion injury by inhibiting renal cell death. Apelin/APJ system involves the progression of diabetic nephropathy (DN). Apelin/APJ system also predicts the process of polycystic kidney disease. Besides, apelin/APJ system prevents some dialysis complications in HD patients. And apelin/APJ system alleviates chronic kidney disease (CKD) by inhibiting vascular calcification (VC). Overall, apelin/APJ system plays diversified roles in kidney disease and may be a potential target for the treatment of kidney disease.