title: Follistatin-like 1 attenuates differentiation and survival of erythroid cells through Smad2/3 signaling.
abstract: Hematopoiesis is a complex process tightly controlled by sets of transcription factors in a context-dependent and stage-specific manner. Smad2/3 transcription factor plays a central role in differentiation and survival of erythroid cells. Here we report that follistatin-like 1 (FSTL1) treatment impairs hemin-induced erythroid differentiation and cell survival. FSTL1 differentially regulates transforming growth factor beta (TGF-β) and bone morphogenetic protein (BMP) signaling. Blockade of Smad2/3 signaling with the ALK5/type I TGF-βR kinase inhibitor, SB-525334, was efficacious for rescue of erythroid differentiation blockage and apoptosis. Reversely, activation of Smad1/5/8 signaling with BMP4 cannot rescue FSTL1-mediated erythroid differentiation blockage and apoptosis. Collectively, these data provide mechanistic insight into the regulation of erythropoiesis by FSTL1 signaling and lay a foundation for exploring FSTL1 signaling as a therapeutic target for anemia.
authors.affiliation: Orthopedic Department, The Second Affiliated Hospital of Soochow University, Suzhou 215000, PR China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Wu
authors.affiliation: Cam-Su Genomic Resource Center, Soochow University, Suzhou 215123, PR China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Soochow University, Suzhou 215006, PR China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Teng
authors.affiliation: Orthopedic Department, The Second Affiliated Hospital of Soochow University, Suzhou 215000, PR China.
authors.forename: Maohua
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Soochow University, Suzhou 215006, PR China. Electronic address: shenzysd@163.com.
authors.forename: Zhenya
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Soochow University, Suzhou 215006, PR China. Electronic address: chenweiqian@suda.edu.cn.
authors.forename: Weiqian
authors.initials: W
authors.lastname: Chen
mesh_terms: D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism*; D004920:Erythropoiesis / Q000502:physiology*; D038702:Follistatin-Related Proteins / Q000378:metabolism*; D006427:Hemin / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D015398:Signal Transduction; D051899:Smad2 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051900:Smad3 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D038702:Follistatin-Related Proteins; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; C448799:FSTL1 protein, human; D006427:Hemin
keywords: Cell survival; Differentiation; Erythroid cells; Erythropoiesis; FSTL1; Smad2/3