Apelin (APLN), an endogenous ligand of the G protein-coupled receptor APJ (APLNR), is involved in a variety of physiological and pathological functions [2]. It is part of the APLN/APJ axis, which has been implicated in multiple biological processes. APLN is also considered an adipokine, with potential roles in metabolism [4].

In a murine and human diabetic model, hyper-activation of the APLN/APJ axis in Sertoli cells was found. High glucose treatment led to local production of APLN by Sertoli cells, which suppressed carnitine production and repressed cell adhesion gene expression, resulting in blood-testis barrier (BTB) structural dysfunction. Blocking APLN/APJ with the small molecule antagonist ML221 significantly ameliorated BTB damage and improved spermatogenesis in diabetic db/db mice and cultured human testes [1]. In esophageal cancer cells, inhibition of APLN by siRNA-APLN reduced proliferative, migrative, and invasive abilities and promoted cell apoptosis, potentially through activating the PI3K/mTOR signaling pathway [3].

In conclusion, APLN plays diverse roles in different biological processes and disease conditions. The study of APLN in gene-modified mouse models, such as in the diabetic db/db mice, has revealed its role in spermatogenesis impairment and BTB dysfunction in diabetes. In cancer, especially esophageal cancer, loss-of-function experiments suggest APLN could be a potential target for treatment. These findings highlight the importance of APLN in both reproductive and cancer-related pathologies.

References:

1. Song, Ke, Yang, Xinyan, An, Geng, Liu, Zhaoting, Zhao, Xiao-Yang. 2022. Targeting APLN/APJ restores blood-testis barrier and improves spermatogenesis in murine and human diabetic models. In Nature communications, 13, 7335. doi:10.1038/s41467-022-34990-3. https://pubmed.ncbi.nlm.nih.gov/36443325/

2. Lv, Shuangyu, An, Yang, Dong, Huan, Yan, Zhongyi, Guo, Xiangqian. 2022. High APLN Expression Predicts Poor Prognosis for Glioma Patients. In Oxidative medicine and cellular longevity, 2022, 8393336. doi:10.1155/2022/8393336. https://pubmed.ncbi.nlm.nih.gov/36193059/

3. Wang, Yuhan, Wang, Gang, Liu, Xiaojun, Yang, Xiwen, Zhang, Ming. 2022. Inhibition of APLN suppresses cell proliferation and migration and promotes cell apoptosis in esophageal cancer cells in vitro, through activating PI3K/mTOR signaling pathway. In European journal of histochemistry : EJH, 66, . doi:10.4081/ejh.2022.3336. https://pubmed.ncbi.nlm.nih.gov/35920446/

4. Fève, Bruno, Bastard, Claire, Fellahi, Soraya, Bastard, Jean-Philippe, Capeau, Jacqueline. 2016. New adipokines. In Annales d'endocrinologie, 77, 49-56. doi:10.1016/j.ando.2016.01.001. https://pubmed.ncbi.nlm.nih.gov/26852251/