Emerging roles of APLN and APELA in the physiology and pathology of the female reproductive system

Liu, Xiaofei; Song, Zifan; Shen, Xin; Lu, Sen; Ling, Yan; Kuang, Haibin

doi:10.7717/peerj.10245

Cited by 10 publications

(9 citation statements)

References 101 publications

(120 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the current study, we revealed that APELA supports the self-renewal of GSCs and negatively regulates cAMP-induced neuronal differentiation. APELA inhibits differentiation probably by suppressing the activity of adenylate cyclase that catalyzes the conversion of ATP to cAMP [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Disruption of β-catenin-mediated negative feedback reinforces cAMP-induced neuronal differentiation in glioma stem cells

et al. 2022

View full text Add to dashboard Cite

Accumulating evidence supports the existence of glioma stem cells (GSCs) and their critical role in the resistance to conventional treatments for glioblastoma multiforme (GBM). Differentiation therapy represents a promising alternative strategy against GBM by forcing GSCs to exit the cell cycle and reach terminal differentiation. In this study, we demonstrated that cAMP triggered neuronal differentiation and compromised the self-renewal capacity in GSCs. In addition, cAMP induced negative feedback to antagonize the differentiation process by activating β-catenin pathway. Suppression of β-catenin signaling synergized with cAMP activators to eliminate GSCs in vitro and extended the survival of animals in vivo. The cAMP/PKA pathway stabilized β-catenin through direct phosphorylation of the molecule and inhibition of GSK-3β. The activated β-catenin translocated into the nucleus and promoted the transcription of APELA and CARD16, which were found to be responsible for the repression of cAMP-induced differentiation in GSCs. Overall, our findings identified a negative feedback mechanism for cAMP-induced differentiation in GSCs and provided potential targets for the reinforcement of differentiation therapy for GBM.

show abstract

Section: Discussionmentioning

confidence: 99%

Disruption of β-catenin-mediated negative feedback reinforces cAMP-induced neuronal differentiation in glioma stem cells

et al. 2022

View full text Add to dashboard Cite

show abstract

“…However, we found that APJ silencing in apelin‐overexpression lung cancer cells did not completely inhibit apelin‐mediated cell proliferation. Although APJ is the only known receptor for apelin, it remains possible that apelin might act in lung cancer cells by another signaling pathway 38,39 . Apelin‐induced activation of APJ suppresses the expression of active SREBP1 and lipid accumulation in hepatocytes 40 .…”

Section: Discussionmentioning

confidence: 99%

“…Although APJ is the only known receptor for apelin, it remains possible that apelin might act in lung cancer cells by another signaling pathway. 38 , 39 Apelin‐induced activation of APJ suppresses the expression of active SREBP1 and lipid accumulation in hepatocytes. 40 These research results imply a functional role of the apelin‐APJ receptor complex in inhibiting adipogenesis.…”

Section: Discussionmentioning

confidence: 99%

Apelin‐mediated deamidation of HMGA1 promotes tumorigenesis by enhancing SREBP1 activity and lipid synthesis

Zhu

Yang

et al. 2022

Cancer Science

View full text Add to dashboard Cite

Enhanced fatty acid synthesis provides proliferation and survival advantages for tumor cells. Apelin is an adipokine, which serves as a ligand of G protein–coupled receptors that promote tumor growth in malignant cancers. Here, we confirmed that apelin increased sterol regulatory element–binding protein 1 (SREBP1) activity and induced the expression of glutamine amidotransferase for deamidating high‐mobility group A 1 (HMGA1) to promote fatty acid synthesis and proliferation of lung cancer cells. This post‐translational modification stabilized the HMGA1 expression and enhanced the formation of the apelin‐HMGA1‐SREBP1 complex to facilitate SREBP1 activity for lipid metabolism and lung cancer cell growth. We uncovered the pivotal role of apelin‐mediated deamidation of HMGA1 in lipid metabolism and tumorigenesis of lung cancer cells.

show abstract

“…In recent years, the involvement and role of adipokines are emerging to the forefront in the field of fertility and reproduction. Many studies suggested that adipokines such as leptin (Spicer, 2001; Tersigni et al, 2011), visfatin (Annie et al, 2020; Reverchon et al, 2013), resistin (Maillard et al, 2011; Niles et al, 2012; Reverchon et al, 2013), adiponectin (Chabrolle et al, 2007; Ledoux et al, 2006; Lord et al, 2005; Schmidt et al, 2008; Takemura et al, 2006), chemerin (Carlino et al, 2012; Goralski et al, 2007; Reverchon et al, 2012) and apelin (Kurowska et al, 2018; Roche et al, 2016; Shokrollahi et al, 2022; Wang et al, 2020) are expressed and play important role in ovary, uterus, placenta. Apelin is expressed in various types of tissues and organs such as the central nervous system and peripheral tissues, including the hypothalamus, adipose tissue, skeletal muscle, digestive system, ovary, uterus, placenta and mammary gland (Cobellis et al, 2007; Mercati et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…The expression of apelin/APJ in granulosa cells, thecal cells and luteal cells of ovary in bovine (Shimizu et al, 2009) and ewes (Mercati et al, 2019) have shown to be elevated with follicular growth. It has been shown that apelin regulates steroidogenesis of granulosa cells and corpus luteum, as an auto/paracrine factor (Różycka et al, 2018;Shokrollahi et al, 2022;Wang et al, 2020). It has also been shown that apelin regulates steroidogenesis via 3β HSD, AMPKa activation and Akt and MAPK3/1 signaling (Rak et al, 2017;Roche et al, 2016Roche et al, , 2017.…”

Section: Introductionmentioning

confidence: 99%

Postnatal developmental expression and localization of apelin and apelin receptor protein in the ovary and uterus of mice

Anima

Gurusubramanian

Roy

2022

Molecular Reproduction Devel

View full text Add to dashboard Cite

Postnatal ovarian and uterine development is crucial to accomplished female fertility. Thus, the investigations of factors that present in pre-pubertal stages are important as it might be responsible for the regulation of ovarian and uterine function. Apelin, an adipokine and its receptor (APJ) are present in female reproductive organs. However, no study has reported its postnatal expression in uterus and ovary. Thus, we investigated the postnatal developmental changes in expression and localization of apelin and APJ in the ovary and uterus of mice.Postnatal ovary and uterus were collected from postnatal day (PND) 1, 7, 14, 21, 42, 65 and performed western blot analysis and immunohistochemistry. Uterine APJ is elevated in PND14 and PND65, whereas, ovarian APJ elevated in PND7, PND14, and PND65. Apelin expression in both ovary and uterus showed intense staining at PND65 and PND14. Our results showed that apelin and APJ abundance was lower at PND21 in uterus and ovary. In conclusion, apelin and APJ are developmentally regulated in the ovary and uterus, and its localization in the different compartments of ovary and uterus suggest its distribution specific physiological role in the uterus and ovary.

show abstract

Emerging roles of APLN and APELA in the physiology and pathology of the female reproductive system

Cited by 10 publications

References 101 publications

Disruption of β-catenin-mediated negative feedback reinforces cAMP-induced neuronal differentiation in glioma stem cells

Disruption of β-catenin-mediated negative feedback reinforces cAMP-induced neuronal differentiation in glioma stem cells

Apelin‐mediated deamidation of HMGA1 promotes tumorigenesis by enhancing SREBP1 activity and lipid synthesis

Postnatal developmental expression and localization of apelin and apelin receptor protein in the ovary and uterus of mice

Contact Info

Product

Resources

About