Aquaporin 1 as a target of Astragalus Polysaccharides alleviates transport stress-induced renal ion homeostasis disorders in newly hatched chickens

Abstract

Transport stress (TS) caused adverse health outcomes that include body weight loss, dehydration, and renal impairment, possibly stemming from the disorder of ions and water homeostasis. Astragalus Polysaccharides (APS), the bioactive substances extracted from the dried roots of Astragalus membranaceus, have been shown to exhibit an anti-stress effect. However, the role of APS in TS-induced renal pathological processes remains unclear. To explore the role of APS in TS-induced adverse effects on kidneys, chicks (d1) were administered with either sterile water or APS and then subjected to simulated TS treatment on a running constant temperature incubator shaker (0.1 ×g rcf). TS increased KIM1 and NGAL levels, decreased ATPase (Na⁺- K⁺- ATPase, Ca²⁺- Mg²⁺- ATPase, Ca²⁺- ATPase, and Mg²⁺- ATPase) activity and aquaporins (AQPs) expression, disrupted ion (Na⁺, K⁺, Cl^-, Ca²⁺and Mg²⁺) homeostasis, resulting in renal injury of chicks. Notably, APS reversed TS - induced ion homeostasis disorder by selectively regulating the expression of ion channels and AQPs. Further, with principal component analysis and cellular thermal shift assay (CETSA), Aquaporin 1 (AQP1) was screened as a novel target of APS. This study highlights the significant role of APS in developing potential therapeutic molecules to manage TS syndrome via targeting of AQP1.

Keywords: Aquaporin 1; Astragalus polysaccharide; Ion homeostasis.