Placensin is a glucogenic hormone secreted by human placenta

Yu, Yiping; He, Jianyong; Hu, Linli; Jiang, Linlin; Fang, Lanlan; Yao, Guidong; Wang, Sijia; Yang, Qingling; Guo, Yanjie; Lin, Li-Ting; Shang, Trisha; Sato, Yoji; Kawamura, Kazuhiro; Hsueh, Aaron J. W.; Sun, Yingpu

doi:10.15252/embr.201949530

Cited by 30 publications

(32 citation statements)

References 65 publications

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“…Manual inspection showed that MER41-associated SRF peaks near these two genes in serum-treated hTSCs have evident H3K27ac occupancy in human placenta (Figure 5F,G). Both FBN2 and CLEC3B have placentaenriched expression ( Figure S13), and interestingly FBN2 was recently reported to secrete a peptide hormone, placensin, that promotes placental cell invasiveness (Yu, et al 2020). Together, our results suggest that specific MER41 elements may facilitate the expression of some human placenta specific genes by creating SRF-bound enhancers.…”

Section: Mer41 Insertion Events Create Lineage-specific Srf Binding Lsupporting

confidence: 60%

“…Specifically, the associated gene FBN2 is a placenta-specific gene recently reported to secrete the peptide hormone placensin which promotes placental cell invasiveness (Yu, et al 2020). Notably, FBN2 is highly expressed in the placenta of human but not mouse (Yu, et al 2020), and higher degree of trophoblast invasion is a remarkable feature for human placenta relative to other species (Cohen and Bischof 2007). These results indicate the possible contribution of MER41 elements in driving the evolution of invasive potential of human placenta by creating lineage-specific enhancers.…”

Section: Discussionmentioning

confidence: 87%

“…We demonstrate that SRF binds dozens of MER41A/B elements, and genes adjacent to MER41-associated SRF peaks usually have increased expression in the placenta of human relative to mouse. Specifically, the associated gene FBN2 is a placenta-specific gene recently reported to secrete the peptide hormone placensin which promotes placental cell invasiveness (Yu, et al 2020). Notably, FBN2 is highly expressed in the placenta of human but not mouse (Yu, et al 2020), and higher degree of trophoblast invasion is a remarkable feature for human placenta relative to other species (Cohen and Bischof 2007).…”

Section: Discussionmentioning

confidence: 99%

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Deciphering the evolution of the transcriptional and regulatory landscape in human placenta

Sun

Wolf

Wang

et al. 2020

Preprint

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In mammals, the placenta mediates maternal-fetal nutrient and waste exchange and provides immunomodulatory actions that facilitate maternal-fetal tolerance. The placenta is highly diversified among mammalian species, yet the molecular mechanisms that distinguish the placenta of human from other mammals are not fully understood. Using an interspecies transcriptomic comparison of human, macaque, and mouse term placentae, we identified hundreds of genes with lineage-specific expression - including dozens that are placentally-enriched and potentially related to pregnancy. We further annotated the enhancers for different human tissues using epigenomic data and demonstrate that the placenta and chorion are unique in that their enhancers display the least conservation. We identified numerous lineage-specific human placental enhancers, and found they are highly overlapped with specific families of endogenous retroviruses (ERVs), including MER21A, MER4A/B and MER39B that were previously linked to immune response and placental function. Among these ERV families, we further demonstrate that MER41 insertions create dozens of lineage-specific Serum Response Factor (SRF) binding loci in human, including one adjacent to FBN2, a placenta-specific gene with increased expression in humans that produces the peptide hormone placensin to stimulate glucose secretion and trophoblast invasion. Our results demonstrate the prevalence of lineage-specific human placental enhancers which are frequently associated with ERV insertions and likely facilitated the lineage-specific evolution of the mammalian placenta.

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Section: Mer41 Insertion Events Create Lineage-specific Srf Binding Lsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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Deciphering the evolution of the transcriptional and regulatory landscape in human placenta

Sun

Wolf

Wang

et al. 2020

Preprint

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“…Of particular interest is FBN2. A recent report published by Yu Y et al [ 48 ] mentions that FBN1 encodes asprosin, a glucogenic hormone, following furin cleavage of the C-terminus of profibrillin. They identified a peptide hormone, placensin encoded by FBN2 in trophoblasts of human placenta.…”

Section: Resultsmentioning

confidence: 99%

Potential SARS-CoV-2 interactions with proteins involved in trophoblast functions – An in-silico study

et al. 2021

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Background Though a large number of pregnant females have been affected by COVID-19, there is a dearth of information on the effects of SARS-CoV-2 infection on trophoblast function. We explored in silico , the potential interactions between SARS-CoV-2 proteins and proteins involved in the key functions of placenta. Methods Human proteins interacting with SARS-CoV-2 proteins were identified by Gordon et al. (2020). Genes that are upregulated in trophoblast sub-types and stages were obtained by gene-expression data from NCBI-GEO and by text-mining. Genes altered in pathological states like pre-eclampsia and gestational diabetes mellitus were also identified. Genes crucial in placental functions thus identified were compared to the SARS-CoV-2 interactome for overlaps. Proteins recurring across multiple study scenarios were analyzed using text mining and network analysis for their biological functions. Results The entry receptors for SARS-CoV-2 – ACE2 and TMPRSS2 are expressed in placenta. Other proteins that interact with SARS-CoV-2 like LOX, Fibulins-2 and 5, NUP98, GDF15, RBX1, CUL3, HMOX1, PLAT, MFGE8, and MRPs are vital in placental functions like trophoblast invasion and migration, syncytium formation, differentiation, and implantation. TLE3, expressed across first trimester placental tissues and cell lines, is involved in formation of placental vasculature, and is important in SARS-CoV (2003) budding and exit from the cells by COPI vesicles. Conclusion SARS-CoV-2 can potentially interact with proteins having crucial roles in the placental function. Whether these potential interactions identified in silico have effects on trophoblast functions in biological settings needs to be addressed by further in vitro and clinical studies.

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“…These diverse GOF and LOF tools also emphasize the high reproducibility of asprosin biology given that the proof obtained from such varied approaches bypasses technical difficulties inherent to any specific reagent/method such as recombinant proteins. To underscore this point, four outside groups have by now replicated asprosin’s physiological effects in vivo ( Li et al, 2019 ; Yu et al, 2020 ; Hekim, 2021 ; Zhang et al, 2021 ), and also expanded asprosin biology beyond our discoveries (modulation of muscle AMPK, identification of the liver asprosin receptor OR4M1, identification of a new asprosin-like hormone derived from FBN2, placensin). This is particularly important given the inability of one group (von Herrath et al) to generate active recombinant asprosin ( von Herrath et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Asprosin-neutralizing antibodies as a treatment for metabolic syndrome

Mishra

Duerrschmid

et al. 2021

eLife

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Background:Recently, we discovered a new glucogenic and centrally acting orexigenic hormone – asprosin. Asprosin is elevated in metabolic syndrome (MS) patients, and its genetic loss results in reduced appetite, leanness, and blood glucose burden, leading to protection from MS.Methods:We generated three independent monoclonal antibodies (mAbs) that recognize unique asprosin epitopes and investigated their preclinical efficacy and tolerability in the treatment of MS.Results:Anti-asprosin mAbs from three distinct species lowered appetite and body weight, and reduced blood glucose in a dose-dependent and epitope-agnostic fashion in three independent MS mouse models, with an IC50 of ~1.5 mg/kg. The mAbs displayed a half-life of over 3days in vivo, with equilibrium dissociation-constants in picomolar to low nanomolar range.Conclusions:We demonstrate that anti-asprosin mAbs are dual-effect pharmacologic therapy that targets two key pillars of MS – over-nutrition and hyperglycemia. This evidence paves the way for further development towards an investigational new drug application and subsequent human trials for treatment of MS, a defining physical ailment of our time.Funding:DK118290 and DK125403 (R01; National Institute of Diabetes and Digestive and Kidney Diseases), DK102529 (K08; National Institute of Diabetes and Digestive and Kidney Diseases), Caroline Wiess Law Scholarship (Baylor College of Medicine, Harrington Investigatorship Harrington Discovery Institute at University Hospitals, Cleveland); Chao Physician Scientist Award (Baylor College of Medicine); RP150551 and RP190561 (Cancer Prevention and Research Institute of Texas [CPRIT]).

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Placensin is a glucogenic hormone secreted by human placenta

Cited by 30 publications

References 65 publications

Deciphering the evolution of the transcriptional and regulatory landscape in human placenta

Deciphering the evolution of the transcriptional and regulatory landscape in human placenta

Potential SARS-CoV-2 interactions with proteins involved in trophoblast functions – An in-silico study

Asprosin-neutralizing antibodies as a treatment for metabolic syndrome

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