Abstract
Antimicrobial peptides (AMPs) are traditionally known to be essential components in host defense via their broad activities against bacteria, fungi, viruses, and protozoa. Their immunomodulatory properties have also recently received considerable attention in mammalian somatic tissues of various species. However, little is known regarding the role of AMPs in the development and maturation of ovarian follicles. Protegrin-1 (PG-1) is an antimicrobial peptide which is known to have potent antimicrobial activity against both gram positive and negative bacteria. Here we report that the PG-1 is present in the porcine ovarian follicular fluid. Treatment of granulosa cell with PG-1 enhanced granulosa cell proliferation in a dose-dependent manner. This is accompanied by increased expression of cell-cycle progression-related genes such as cyclin D1(CCND1), cyclin D2 (CCND2), and cyclin B1(CCNB1). Additionally, Western blot analysis showed that PG-1 increased phosphorylated epidermal growth factor receptor (EGFR), and the phosphorylated-/total extracellular signal-regulated kinase (ERK)1/2 ratio. Pretreatment with either U0126, a specific ERK1/2 phosphorylation inhibitor, or EGFR kinase inhibitor, AG1478, blocked the PG-1 induced proliferation. Moreover, luciferase reporter assay revealed that ETS domain-containing protein-1 (Elk1) C/EBP homologous protein (CHOP), and the transcription activators downstream of the MAPK pathway, were activated by PG-1. These data collectively suggest that PG-1 may regulate pig granulosa cell proliferation via EGFR-MAPK pathway., Hence, our finding offers insights into the role of antimicrobial peptides on follicular development regulation.
Highlights
Antral follicle is characterized by a fluid-filled cavity, termed as antrum adjacent to the oocyte and the surrounding granulosa cells
Granulosa cell proliferation is closely related to the cell cycle process which is tightly controlled by cyclin-dependent kinases (Cdks) and their interactions with cyclins and Cdk inhibitors (Golias et al, 2004)
We further examined whether PG-1 regulates the expression of genes associated with granulosa cell proliferation
Summary
Antral follicle is characterized by a fluid-filled cavity, termed as antrum adjacent to the oocyte and the surrounding granulosa cells. PG-1 Regulates Granulosa Cell Proliferation to the size increase of small antral follicles, which is a necessary process of follicular development (Fortune, 1994). Granulosa cell proliferation is closely related to the cell cycle process which is tightly controlled by cyclin-dependent kinases (Cdks) and their interactions with cyclins and Cdk inhibitors (Golias et al, 2004). These Cdks and Cdk inhibitors play a role in the regulation of granulosa cell proliferation
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