Neuregulin-1 signaling regulates cytokines and chemokines expression and secretion in granulosa cell

Abstract

Background Granulosa cells (GCs) are multilayered somatic cells within the follicle that provide physical support and microenvironment for the developing oocyte. In recent years, the role of Neuregulin-1 (NRG1), a member of the EGF-like factor family, has received considerable attention due to its neurodevelopmental and cardiac function. However, the exact physiological role of NRG1 in GC is mainly unknown. In order to confirm that NRG1 plays a regulatory role in rat GC functions, endogenous NRG1-knockdown studies were carried out in GCs using RNA interference methodology. Results Knockdown of NRG1 in GCs resulted in the enhanced expression and secretion of the cytokines and chemokines. In addition, the phosphorylation of PI3K/Akt/ERK1/2 was significantly low in GCs under these experimental conditions. Moreover, in vitro experimental studies suggest that tumor necrosis factor-α (TNFα) treatment causes the physical destruction of GCs by activating caspase-3/7 activity. In contrast, exogenous NRG1 co-treatment of GCs delayed the onset of TNFα-induced apoptosis and inhibited the activation of caspase-3/7 activity. Furthermore, current experimental studies suggest that gonadotropins promote differential expression of NRG1 and ErbB3 receptors in GCs of the antral follicle. Interestingly, NRG1 and ErbB3 were intensely co-localized in the mural and cumulus GCs and cumulus-oocyte complex of pre-ovulatory follicles in the estrus stage. Conclusions The present studies suggest that gonadotropins-dependent NRG1-signaling in GCs may require the balance of the cytokines and chemokines expression and secretion, ultimately which may be supporting the follicular maturation and oocyte competence for ovulation and preventing follicular atresia.

Prediction and Validation of Hub Genes Related to Major Depressive Disorder Based on Co-expression Network Analysis

“…Furthermore, inflammatory pathways are altered or inactivated by exogenous NRG1 treatments related to the tissue damage during ischemic episodes [61][62][63]. It was recently reported that cytokines and chemokines expression and secretion are regulated by NRG1 signaling [69]. Besides, Nedd4l-mediated downregulation of NRG1 plays a vital role in mice's depression-like phenotypes in chronic social defeat stress [70], in line with our outcomes.…”

Facilitation of Ovarian Response by Mechanical Force—Latest Insight on Fertility Improvement in Women with Poor Ovarian Response or Primary Ovarian Insufficiency

“…In the ovary, Nrg1 expression in granulosa cells is induced by LH. Studies using Nrg1-knockdown and exogenous Nrg1 treatment showed the gonadotropins-dependent Nrg1 signaling in granulosa cells is important for supporting follicular growth and oocyte meiotic maturation [210]. Consistently, targeted disruption of Nrg1 in granulosa cells of gcNrg1KO mice reduces the number of pups per litter, perhaps due to aberrant regulation of protein kinase C signaling in cumulus cells [211,212].…”

Analysis on the pathogenesis and treatment progress of NRG1 fusion-positive non-small cell lung cancer

“…Increased NRG1 expression can activate downstream signaling pathways, such as the ERBB2/ ERBB3 pathway, which promotes cancer cell proliferation, migration, and survival (12). Notably, NRG1 expression can be modulated by various factors, including growth factors, hormones, and environmental stimuli (13)(14)(15)(16). Dysregulation of NRG1 expression can occur through genetic alterations, epigenetic changes, or altered transcriptional regulation, leading to its involvement in cancer development and progression.…”