Growth Hormone Releasing Peptide-2 Attenuation of Protein Kinase C-Induced Inflammation in Human Ovarian Granulosa Cells

Abstract

Cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) are two important inflammatory mediators in ovulation. Ghrelin may modulate inflammatory signaling via growth hormone secretagogue receptors. We investigated the role of ghrelin in KGN human ovarian granulosa cells using protein kinase C (PKC) activator phorbol 12, 13-didecanoate (PDD) and synthetic ghrelin analog growth hormone releasing peptide-2 (GHRP-2). GHRP-2 attenuated PDD-induced expression of protein and mRNA, the promoter activity of COX-2 and IL-8 genes, and the secretion of prostaglandin E2 (PGE2) and IL-8. GHRP-2 promoted the degradation of PDD-induced COX-2 and IL-8 proteins with the involvement of proteasomal and lysosomal pathways. PDD-mediated COX-2 production acts via the p38, c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways; PDD-mediated IL-8 production acts via the p38, JNK and ERK pathways. GHRP-2 reduced the PDD-induced phosphorylation of p38 and JNK and activator protein 1 (AP-1) reporter activation and PDD-induced NF-κB nuclear translocation and reporter activation. The inhibitors of mitogen-activated protein kinase phosphatase-1 (MKP-1) and protein phosphatase 2 (PP2A) reduced the inhibitory effect of GHRP-2 on PDD-induced COX-2 and IL-8 expression. Our findings demonstrate an anti-inflammatory role for ghrelin (GHRP-2) in PKC-mediated inflammation of granulosa cells, at least in part, due to its inhibitory effect on PKC-induced activation of p38, JNK and NF-κB, possibly by targeting to MKP-1 and PP2A.

miR-128-3p Regulates Follicular Granulosa Cell Proliferation and Apoptosis by Targeting the Growth Hormone Secretagogue Receptor

“…Therefore, KGN cells are considered a valuable model for the study of steroidogenesis, cell growth, and apoptosis regulation in human GCs [ 57 , 58 ]. Furthermore, it has been discovered that KGN cells express the GHSR gene and are responsive to stimulation by ghrelin analog growth hormone-releasing peptide-2 [ 59 ]. Therefore, this study selected KGN cells to explore the relationship between miR-128-3p and GHSR gene expression and their effects on the proliferation and apoptosis of KGN cells.…”

Andrographolide Inhibits PMA-Induced EPCR Shedding through JNK and p38 MAPK

“…PMA can exert effects by the phosphorylation of mitogen-activated protein kinases (MAPKs), such as extracellular regulated protein kinase (ERK) 1/2, p38 and c-Jun N-terminal kinase (JNK) (Shankar et al 2016;Chao et al 2016;Chen et al 2019).…”

Ghrelin is associated with anti‐mullerian hormone levels in Chinese systemic lupus erythematosus

“…Besides, ghrelin may influence ovarian steroidogenesis and oocyte maturation 8,9 . More recently researches reported that ghrelin may also have direct effects ovarian granulosa cells to influence the expression of Anti‐Mullerian hormone (AMH) 10 …”

“…wileyonlinelibrary.com/journal/aji 1 of 6 https://doi.org/10.1111/aji.13579 ovarian granulosa cells to influence the expression of Anti-Mullerian hormone (AMH). 10 AMH is a peptide growth factor belongs to the transforming growth factor-β (TGF-β) family, and is produced by granulosa cells of growing follicles. 11 AMH levels are unaffected by hormonal contraceptives, more sensitive and specific than other measures of ovarian reserve.…”