MAPK signaling pathway participates in the regulation of intestinal phosphorus and calcium absorption in broiler chickens via 1,25-dihydroxyvitamin D3

Four experiments were performed to investigate the role of the mitogen-activated protein kinase (MAPK) signaling pathway in intestinal absorption of phosphorus (P) and calcium (CA) in broiler chickens. Experiment 1 assessed how dietary levels of 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) influence the gene expression of intestinal P and CA transporters in broilers. Experiment 2 evaluated the effects of 1,25(OH)₂D₃ administered via intraperitoneal injection on the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38MAPK) signaling pathways. Experiments 3 and 4 investigated the effect of ERK and p38MAPK inhibitors on the expression of intestinal P and CA transporters. The findings demonstrated that broilers (1-21 days old) fed a 1,25(OH)₂D₃-deficient diet (0.625 µg/kg) exhibited reduced body weight, tibia P and CA levels, and mRNA levels of P transporters (NaPi-IIb, PiT-1, and PiT-2), CA transporters (NCX1, PMCA1b, and CaBP-D28k), vitamin D receptors (VDR), ERK, and p38MAPK in the duodenum (Experiment 1) (P < 0.05). By comparison, the growth, bone quality, and mRNA levels of genes (except for duodenal NaPi-IIb) in broilers were similar to those in broilers fed the control diet when dietary 1,25(OH)₂D₃ was adequate (5 µg/kg) (Experiment 1) (P > 0.05). After intraperitoneal injection of 1,25(OH)₂D₃, the mRNA level of jejunal NaPi-IIb and the protein level of p-p38MAPK/t-p38MAPK in broilers (9-14 days old) decreased (P < 0.05), whereas the mRNA level of CaBP-D28k and the protein level of p-ERK/t-ERK increased (Experiment 2) (P < 0.05). The mRNA and protein expression of jejunal NaPi-IIb and the protein expression of CaBP-D28k in broilers (9-17 days old) treated with the ERK Inhibitor PD98059 were greater than those in the control group (Experiment 3) (P < 0.05). Similarly, compared with control broilers, broilers (9-17 days old) treated with the p38MAPK inhibitor SB203580 showed elevated mRNA expression of jejunal NaPi-IIb and CaBP-D28k (Experiment 4) (P < 0.05). These results suggest that adequate supplementation with 1,25(OH)₂D₃ (5 µg/kg) can restore broiler growth and bone quality by upregulating the transcription of genes involved in intestinal P and CA absorption. Additionally, the ERK and p38MAPK signaling pathways are implicated in the modulatory effect of 1,25(OH)₂D₃ on the absorption of P and CA in broilers.