Apelin (APLN), an endogenous ligand of the G protein-coupled receptor APJ (APLNR), is involved in various physiological and pathological functions [4]. It is part of the APLN/APJ axis, which has been linked to multiple biological processes such as angiogenesis, macrophage function regulation, and metabolism [2,3]. APLN has been associated with numerous diseases, making it an important gene for research, and genetic models can be valuable in further elucidating its functions.

In a murine diabetic model, high glucose treatment led Sertoli cells to produce APLN, which suppressed carnitine production and cell adhesion gene expression in Sertoli cells, ultimately causing blood-testis barrier (BTB) structural dysfunction. Blocking the APLN/APJ axis with the small molecule antagonist ML221 significantly improved BTB damage and spermatogenesis in diabetic db/db mice, and these findings were also validated in cultured human testes [1]. In esophageal cancer cells, inhibition of APLN by siRNA-APLN reduced cell proliferation, migration, and invasion, and promoted apoptosis, which could be restored by overexpressing APLN. Knocking down APLN also suppressed the PI3K/mTOR signaling pathway, suggesting APLN could be a potential target for esophageal cancer treatment [5].

In conclusion, APLN is a key molecule involved in multiple biological processes. The use of gene-knockout or conditional-knockout mouse models, as seen in the diabetic and esophageal cancer studies, has revealed its role in disease-related processes such as spermatogenesis in diabetes and cancer cell behavior in esophageal cancer. These findings provide potential therapeutic targets for these diseases.