Role of cellular retinol-binding protein, type 1 and retinoid homeostasis in the adult mouse heart: a multi-omic approach

ABSTRACT: The main active metabolite of Vitamin A, all-trans retinoic acid (RA), is responsible for proper cellular function and tissue organization. The role of RA has been extensively studied in development, but there is limited research on its role in the adult heart. Cellular retinol-binding protein, type 1 (CRBP1), encoded by retinol-binding protein, type 1 (Rbp1), regulates RA homeostasis by delivering vitamin A to enzymes for RA synthesis. An animal model of CRBP1 deficiency, such as Rbp1–/– mice, can provide insight into disrupted RA biosynthesis and signaling. In this work, a multi-omics approach was used to characterize the effect of CRBP1 loss. Retinoid homeostasis was disrupted in Rbp1-/- mouse heart tissue, as seen by a 33% and 24% decrease in RA levels in the left and right ventricles, respectively, compared to wild-type mice (WT). To further inform on the effect of disrupted RA homeostasis, we conducted high-throughput targeted metabolomics. A total of 222 metabolite and metabolite combinations were analyzed, with 33 having differential expression between Rbp1-/- and WT hearts. Additionally, we performed global proteome profiling to further characterize the impact of CRBP1 loss in adult mouse hearts. More than 2,606 unique proteins were identified, with 340 proteins having differential expression between Rbp1-/- and WT hearts. Pathway analysis performed on metabolomic and proteomic data revealed pathways related to cellular metabolism and cardiac metabolism were the most disrupted in Rbp1-/- mice. Together, these studies provide data for establishing the effect of dysregulated RA signaling in the adult mouse heart.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

SUBMITTER: Weiliang Huang  

LAB HEAD: Maureen Kane

PROVIDER: PXD029349 | Pride | 2022-10-13

REPOSITORIES: Pride