Follistatin-like 3 (FSTL-3), also known as Follistatin-related Gene (FLRG) and Follistatin-related protein (FSRP), is a 30-35 kDa secreted glycoprotein. FSTL-3 encodes a novel secreted glycoprotein that is highly homologous to follistatin and binds activins and bone morphogenetic proteins, members of the TGF beta superfamily of growth/differentiation factors. FSTL-3 protein inhibits activin-induced and bone morphogenetic protein-2-induced transcriptional responses in a dose-dependent manner, and its mRNA is abundantly expressed in human placenta, trophoblast, heart, uterus, ovary, testis and adrenal gland. Mature human FSTL-3 consists of an Activin and Myostatin binding N-terminal domain, two Follistatin-like domains, and two Kazal-like domains. BMP-2, -6, and -7 do not compete for Activin A binding, and FSTL-3 binds only weakly to Activin B. Unlike Follistatin, FSTL-3 does not contain a heparin-binding domain and does not interact with heparin sulfate proteoglycans. FSTL-3 has been studied in regulation of energy balance and metabolism, gestational diabetes, preeclampsia, and promotor of tumor cell proliferation.

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Follistatin-Like 3 ELISA AL-152
Anastasilakis AD, Polyzos SA, Rodopaios NE, Makras P, Kumar A, Kalra B, Mantzoros CS. Activins, follistatins and inhibins in postmenopausal osteoporosis: A proof of concept, case-control study. Metabolism. 2022 Dec 29:155397. doi: 10.1016/j.metabol.2022.155397. Epub ahead of print. PMID: 36587801.

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Guignabert C, Savale L, Boucly A, Thuillet R, Tu L, Ottaviani M, Rhodes CJ, De Groote P, Prévot G, Bergot E, Bourdin A, Howard LS, Fadel E, Beurnier A, Roche A, Jevnikar M, Jaïs X, Montani D, Wilkins MR, Sitbon O, Humbert M. Serum and Pulmonary Expression Profiles of the Activin Signaling System in Pulmonary Arterial Hypertension. Circulation. 2023 Jun 13;147(24):1809-1822. doi:10.1161/CIRCULATIONAHA.122.061501. Epub 2023 Apr 25. PMID: 37096577.

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Kalra B, Patel A, Kommareddy V, Ganapathy K, Mistry S, Budhavarapu V, Savjani G, Pasternack A, Ritvos O, Hyvonen M, Kumar A. Development of Novel Specific ELISAs for all Inhibins, Activins and their Binding Proteins FST and FSTL3. Poster presented at 98th Annual Endocrine Society Meeting; 2016 Apr 1-3; Boston, MA.

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Kristensen SG, Kumar A, Kalra B, Pors SE, Bøtkjær JA, Mamsen LS, Colmorn LB, Fedder J, Ernst E, Owens LA, Hardy K, Franks S, Andersen CY. Quantitative Differences in TGF-β Family Members Measured in Small Antral Follicle Fluids From Women With or Without PCO. J Clin Endocrinol Metab. 2019 Dec 1;104(12):6371-6384. doi: 10.1210/jc.2019-01094. PMID: 31287539.

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Naseem H, Dreixler J, Mueller A, Tung A, Dhir R, Chibber R, Fazal A, Granger JP, Bakrania BA, deMartelly V, Rana S, Shahul S. Antepartum Aspirin Administration Reduces Activin A and Cardiac Global Longitudinal Strain in Preeclamptic Women. J Am Heart Assoc. 2020 Jun 16;9(12):e015997. doi: 10.1161/JAHA.119.015997. Epub 2020 Jun 4. PMID: 32495688; PMCID: PMC7429043.

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Paajanen J, Ilonen I, Lauri H, Järvinen T, Sutinen E, Ollila H, Rouvinen E, Lemström K, Räsänen J, Ritvos O, Koli K, Myllärniemi M. Elevated Circulating Activin A Levels in Patients With Malignant Pleural Mesothelioma Are Related to Cancer Cachexia and Reduced Response to Platinum-based Chemotherapy. Clin Lung Cancer. 2019 Oct 25. pii: S1525-7304(19)30287-6. doi: 10.1016/j.cllc.2019.10.013. [Epub ahead of print]

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Panagiotou G, Ghaly W, Upadhyay J, Pazaitou-Panayiotou K, Mantzoros CS. Serum Follistatin Is Increased in Thyroid Cancer and Is Associated With Adverse Tumor Characteristics in Humans. J Clin Endocrinol Metab. 2021 Apr 23;106(5):e2137-e2150. doi: 10.1210/clinem/dgab041. PMID: 33493282.

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Panagiotou G, Papakonstantinou E, Vagionas A, Polyzos SA, Mantzoros CS. Serum Levels of Activins, Follistatins, and Growth Factors in Neoplasms of the Breast: A Case-Control Study. J Clin Endocrinol Metab. 2019 Feb 1;104(2):349-358.

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Peradze N, Farr OM, Perakakis N, Lázaro I, Sala-Vila A, Mantzoros CS. Short-term treatment with high dose liraglutide improves lipid and lipoprotein profle and changes hormonal mediators of lipid metabolism in obese patients with no overt type 2 diabetes mellitus: a randomized, placebo-controlled, cross-over, double-…. Peradze et al. Cardiovasc Diabetol (2019) 18:141 https://doi.org/10.1186/s12933-019-0945-7

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Perakakis N, Chen J, Ghaly W, Vamvini MT, Mantzoros CS. Effects of oral and intravenous lipid administration on hormones affecting energy balance. Poster session presented at the Obesity Week Meeting; 2017 Oct 29-Nov 2; Washington DC.

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Perakakis N, Kokkinos A, Peradze N, Tentolouris N, Ghaly W, Tsilingiris D, Alexandrou A, Mantzoros CS. Follistatins in glucose regulation of healthy and obese subjects. Diabetes Obes Metab. 2019 Mar; 21(3): 683–690

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Perakakis N, Mougios V, Fatouros I, Siopi A, Draganidis D, Peradze N, Ghaly W, Mantzoros CS. Physiology of Activins/Follistatins: Associations With Metabolic and Anthropometric Variables and Response to Exercise. J Clin Endocrinol Metab. 2018 Oct 1;103(10):3890-3899.

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Perakakis N, Upadhyay J, Ghaly W, Chen J, Chrysafi P, Anastasilakis AD, Mantzoros CS. Regulation of the activins-follistatins-inhibins axis by energy status: Impact on reproductive function. Metabolism. 2018 May 9. pii: S0026-0495(18)30120-3.

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Perakakis N, Upadhyay J, Ghaly W, Chen J, Mantzoros CS. Leptin-dependent and leptin-independent pathways linking energy sufficiency with reproduction. Poster session presented at the Obesity Week Meeting; 2017 Oct 29-Nov 2; Washington DC.

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Polyzos SA, Perakakis N, Boutari C, Kountouras J, Ghaly W, Anastasilakis AD, Karagiannis A, Mantzoros CS. Targeted Analysis of Three Hormonal Systems Identifies Molecules Associated with the Presence and Severity of NAFLD. J Clin Endocrinol Metab. 2020 Mar 1;105(3):e390–400. doi: 10.1210/clinem/dgz172. PMID: 31690932; PMCID: PMC7112980.

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Roh JD, Castro C, Yu A, Rana S, Shahul S, Gray KJ, Honigberg MC, Ricke-Hoch M, Iwamoto Y, Yeri A, Kitchen R, Guerra JB, Hobson R, Chaudhari V, Chang B, Sarma A, Lerchenmüller C, Al Sayed ZR, Diaz Verdugo C, Xia P, Skarbianskis N, Zeisel A, Bauersachs J, Kirkland JL, Karumanchi SA, Gorcsan J 3rd, Sugahara M, Damp J, Hanley-Yanez K, Ellinor PT, Arany Z, McNamara DM; IPAC Investigators; Hilfiker-Kleiner D, Rosenzweig A. Placental senescence pathophysiology is shared between peripartum cardiomyopathy and preeclampsia in mouse and human. Sci Transl Med. 2024 Apr 17;16(743):eadi0077. doi: 10.1126/scitranslmed.adi0077. Epub 2024 Apr 17. PMID: 38630848; PMCID: PMC11331492.

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Valenzuela-Vallejo L, Chrysafi P, Agraz M, Connelly M, Papatheodoridis G, Verrastro O, Mingrone G, Mantzoros CS. GROWTH DIFFERENTIATION FACTOR 15 (GDF-15) LEVELS IS ASSOCIATED WITH THE PRESENCE AND SEVERITY OF NAFLD. Nutr Diabetes. 2022 Feb 22;12(1):9. doi: 10.1038/s41387-022-00187-2. PMID: 35194014; PMCID: PMC8863897

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