Abstract

Retinol binding protein 4 (RBP4), mainly secreted by the liver and adipocytes, is a transporter of vitamin A. RBP4 has been shown to be involved in several pathophysiological processes, such as obesity, insulin resistance, and cardiovascular risk. Reports have indicated the high expression levels of RBP4 in cystic follicles. However, the role of RBP4 in mammalian follicular granulosa cells (GCs) remains largely unknown. To illustrate the molecular pathways associated with the effects of RBP4 on GCs, we used high-throughput sequencing to detect differential gene expression in GCs overexpressing RBP4. A total of 113 differentially expressed genes (DEGs) were identified in RBP4-overexpressing GCs, and they included 71 upregulated and 42 downregulated genes. The differential expressions of the top 10 DEGs were further confirmed by real-time quantitative polymerase chain reaction. Pathway analysis indicated that the DEGs are mostly involved in oxidative phosphorylation, Parkinson’s disease, non-alcoholic fatty liver disease, Huntington’s disease, cardiac muscle contraction, Alzheimer’s disease, fatty acid biosynthesis, AMP-activated protein kinase signaling pathway, and insulin signaling pathway. Genes in these pathways should be useful for future studies on GCs. Altogether, the results of our study establish a framework for understanding the potential functions of RBP4 in porcine GCs.

Highlights

  • Retinols mediate various reproductive processes, such as follicle development, oocyte maturation, early embryogenesis, and steroidogenesis [1,2,3,4]

  • Retinol binding protein 4 (RBP4) is an adipokine belonging to the lipocalin family of proteins; it plays a role in the transport of retinols from liver and adipose tissues to the blood and other tissues [5,6]

  • The recombinant lentiviral was successfully infected into granulosa cells (GCs)

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Summary

Introduction

Retinols (a metabolite form of vitamin A, ROH) mediate various reproductive processes, such as follicle development, oocyte maturation, early embryogenesis, and steroidogenesis [1,2,3,4]. Retinol binding protein 4 (RBP4) is an adipokine belonging to the lipocalin family of proteins; it plays a role in the transport of retinols from liver and adipose tissues to the blood and other tissues [5,6]. RBP4 exerts its function by binding retinols in blood to form a transient RBP4-ROH complex. STRA6 facilitates the dissociation of retinols from the complex and transports them into cells [8]. RBP4, which is involved in retinol metabolism, has been identified to be associated with numerous metabolic diseases, such as insulin resistance (IR), type 2 diabetes mellitus, obesity, and cardiovascular risk [9,10]. RBP4 expression in adipose tissues is regulated by 17-β-estradiol. RBP4 can drive ovarian cancer cell migration and proliferation through RhoA/Rock and extracellular signal-regulated kinase pathways involving matrix metalloproteinase (MMP) 2 and MMP9 expressions [12]

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