Affinage

FSTL1

Follistatin-related protein 1 · UniProt Q12841

Length
308 aa
Mass
35.0 kDa
Annotated
2026-04-28
100 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FSTL1 is a secreted glycoprotein that functions as a context-dependent modulator of BMP, TGF-β, and Wnt signaling pathways, with broad roles in organogenesis, tissue repair, fibrosis, and immune regulation. Extracellularly, FSTL1 directly binds BMP4 and the BMP receptor ALK6 to antagonize BMP/Smad1/5/8 signaling in lung, ureter, and endocardial development (PMID:21482757, PMID:22485132, PMID:28705792), while it enhances Wnt/β-catenin signaling by bridging Wnt ligands to Frizzled receptors via its EC and VWC domains (PMID:35525270). FSTL1 signals through the cell-surface receptor DIP2A to activate Smad2/3 and Akt independently of TGFβR1, mediating endothelial survival, cardiac angiogenesis, and glioblastoma chemoresistance by blocking DIP2A nuclear translocation and HDAC2-dependent MGMT silencing (PMID:20054002, PMID:33246164, PMID:30542120); it also engages TLR4 to activate NF-κB/AKT/mTOR signaling in tumor cells (PMID:34551961, PMID:28883005). Intracellularly in macrophages, its FK domain binds PKM2 to promote glycolytic reprogramming and M1 polarization driving liver fibrosis (PMID:35140065), and its own expression is controlled by a TGF-β/KSRP-dependent switch that toggles between miR-198 and FSTL1 protein production from a shared transcript (PMID:23395958).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2006 High

    Establishing that FSTL1 is subject to post-transcriptional regulation by tissue-specific miRNAs revealed it as a dynamically controlled gene rather than a constitutively expressed factor.

    Evidence miR-206 target site reporter assay and MyoD-driven fibroblast-to-muscle conversion showing miR-206 suppresses Fstl1 during skeletal muscle differentiation

    PMID:17030984

    Open questions at the time
    • Whether miR-206 regulation of FSTL1 operates in vivo during myogenesis was not tested
    • Other miRNAs targeting FSTL1 were not surveyed
  2. 2010 High

    Identification of DIP2A as a cell-surface receptor for FSTL1 established a direct signaling mechanism through which secreted FSTL1 activates Akt to promote endothelial survival and cardioprotection.

    Evidence Membrane fraction pull-down, reciprocal Co-IP, DIP2A siRNA ablation of FSTL1 binding and downstream Akt phosphorylation in endothelial cells and cardiomyocytes

    PMID:20054002

    Open questions at the time
    • Structural basis of FSTL1-DIP2A interaction unknown
    • Whether DIP2A mediates all FSTL1 functions or only a subset was unresolved
  3. 2011 High

    Demonstrating that FSTL1 directly binds BMP4 and functionally antagonizes BMP/Smad1/5/8 signaling in vivo resolved FSTL1's mechanism as a secreted BMP antagonist essential for lung morphogenesis.

    Evidence Fstl1 knockout mouse with pulmonary atelectasis, Co-IP of Fstl1 with BMP4, Noggin epistasis rescue restoring lung development

    PMID:21482757

    Open questions at the time
    • Relative affinities of FSTL1 for different BMP family ligands not determined
    • Whether FSTL1 antagonism is stoichiometric or catalytic was unclear
  4. 2012 Medium

    Showing that FSTL1 also directly binds the BMP type I receptor ALK6 expanded the antagonism mechanism beyond ligand sequestration to receptor-level inhibition.

    Evidence Direct binding assay of Fstl1 to ALK6, elevated pSmad1/5/8 in Fstl1-null ureters, Fstl1 knockout mouse ureter phenotype

    PMID:22485132

    Open questions at the time
    • Whether FSTL1 blocks BMP-ALK6 association or alters receptor conformation was not distinguished
    • Binding affinity not quantified
  5. 2013 High

    Discovery of the TGF-β/KSRP-controlled molecular switch between miR-198 and FSTL1 protein from a shared transcript revealed an elegant post-transcriptional mechanism coupling wound healing signals to FSTL1 production.

    Evidence Human ex vivo skin organ culture, KSRP knockdown toggling miR-198/FSTL1 output, TGF-β pathway manipulation, migration assays

    PMID:23395958

    Open questions at the time
    • Whether this switch operates in tissues beyond skin was not tested
    • Quantitative kinetics of the switch in vivo unknown
  6. 2017 Medium

    A cluster of studies in 2017 expanded FSTL1's downstream signaling repertoire to include TLR4/NF-κB, autophagy/EMT, Smad3-c-Jun transcriptional regulation of Fstl1 itself, smooth muscle differentiation via myocardin/SRF, and competitive BMP4 sequestration from BMPR2 in glioma, revealing FSTL1 as a pleiotropic factor operating through multiple receptor-pathway axes in different tissues.

    Evidence Conditional Tie2-Cre KO (endocardium), OVA-challenged Fstl1 heterozygous mice (autophagy/EMT), Fstl1 promoter luciferase reporter (Smad3-c-Jun), BMP4-BMPR2 competition Co-IP (glioma), NF-κB/TLR4 inhibitor rescue (ESCC), myocardin/SRF loss in Fstl1 KO lungs

    PMID:28473327 PMID:28495857 PMID:28574994 PMID:28705792 PMID:28827448 PMID:28883005 PMID:29212066

    Open questions at the time
    • Which receptor (DIP2A, TLR4, or others) mediates each tissue-specific effect not systematically resolved
    • Relative contributions of BMP antagonism vs. TLR4 signaling in the same tissue not compared
    • EGF-FSTL1-Wnt7a axis replicated only in HNSCC cells
  7. 2018 High

    Demonstrating that FSTL1 sequesters DIP2A at the cell surface to prevent its nuclear HDAC2 complex formation revealed a non-canonical receptor-blocking mechanism linking FSTL1 to epigenetic regulation of chemoresistance.

    Evidence Co-IP of Fstl1 with DIP2A, subcellular fractionation, ChIP showing increased H3K9Ac at MGMT promoter upon FSTL1 exposure, DIP2A knockdown epistasis, glioblastoma xenograft

    PMID:30542120

    Open questions at the time
    • Whether this DIP2A sequestration mechanism operates at other loci beyond MGMT not tested
    • Structural basis of cytoplasmic DIP2A retention by FSTL1 undefined
  8. 2019 High

    The crystal structure of the FK domain revealed a stable dimer and established this domain as structurally and functionally indispensable for TGF-β signaling, providing the first structural framework for FSTL1 function.

    Evidence X-ray crystallography of murine Fstl1 FK domain, SEC-MALS confirming dimerization, FK domain deletion abolishing TGF-β signaling

    PMID:31351024

    Open questions at the time
    • Full-length FSTL1 structure not solved
    • Whether dimerization is required for receptor engagement unknown
    • Structure of FSTL1 in complex with any binding partner not available
  9. 2020 Medium

    Two studies refined FSTL1's immunomodulatory and angiogenic roles: FSTL1 suppresses NF-κB via Nr4a1 in lung macrophages, and FSTL1 signals through DIP2A-Smad2/3 independently of TGFβR1 to drive cardiac angiogenesis.

    Evidence Recombinant FSTL1 macrophage treatment with Nr4a1-dependent NF-κB readout, FSTL1 hypomorphic mice with emphysema; AAV-FSTL1 in rat MI model with TGFβR1 inhibitor demonstrating DIP2A-Smad2/3 independence

    PMID:31834999 PMID:33246164

    Open questions at the time
    • Direct Nr4a1-FSTL1 binding not demonstrated
    • Whether DIP2A-Smad2/3 and DIP2A-Akt are activated simultaneously or context-dependently not resolved
  10. 2022 High

    Two discoveries in 2022 substantially expanded FSTL1's mechanism: its EC and VWC domains bridge Wnt ligands to Frizzled receptors to enhance Wnt/β-catenin signaling, and its FK domain binds intracellular PKM2 to reprogram macrophage glycolysis and drive M1 polarization, the latter representing the first intracellular signaling function of FSTL1.

    Evidence Domain deletion Co-IP mapping FSTL1-Wnt-FZD4 interactions, TOP/FOP reporter (kidney fibrosis model); myeloid-specific FSTL1 KO mice, FSTL1-PKM2 Co-IP, PKM2 phosphorylation/ubiquitination assays across three liver fibrosis models

    PMID:35140065 PMID:35525270

    Open questions at the time
    • How secreted FSTL1 accesses intracellular PKM2 in macrophages not mechanistically explained
    • Whether Wnt potentiation and BMP antagonism occur simultaneously in the same cell unclear
    • Whether FSTL1-PKM2 interaction occurs in cell types beyond macrophages not tested
  11. 2023 Medium

    Recent work expanded FSTL1's transcriptional regulation (IRF4 in muscle), receptor usage (CD14 as an additional liver receptor), post-transcriptional stabilization (HuR), and downstream effectors (Src kinase for junction opening; SENP1 for deSUMOylation-dependent TGF-β amplification).

    Evidence Muscle-specific IRF4 KO with FSTL1 promoter luciferase and DIP2A/CD14 receptor assignment in liver cell types; HuR siRNA and Src inhibitor in HUVECs; SENP1 knockdown blocking FSTL1-induced senescence via Smad4/Ras deSUMOylation

    PMID:37369969 PMID:37694287 PMID:37770480

    Open questions at the time
    • CD14 as FSTL1 receptor demonstrated only in liver; generality unknown
    • How FSTL1 upregulates SENP1 mechanistically not defined
    • Whether H2S-HuR-FSTL1 axis operates outside endothelial cells not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Critical open questions include: the full-length FSTL1 structure and how domain architecture determines selective receptor engagement; how secreted FSTL1 accesses intracellular PKM2; the hierarchy among DIP2A, TLR4, CD14, and Frizzled as FSTL1 receptors in different tissues; and whether FSTL1 dimerization (via FK domain) is required for specific receptor interactions.
  • No full-length FSTL1 structure available
  • Mechanism of FSTL1 intracellular access for PKM2 binding undefined
  • Systematic receptor selectivity across tissues not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0048018 receptor ligand activity 3 GO:0008289 lipid binding 1
Localization
GO:0005576 extracellular region 7
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3
Partners
ALK6BMP4DIP2AFZD4PKM2TLR4VIM

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 MyoD directly activates transcription of miR-206, which targets sequences in the Fstl1 3' UTR and suppresses Fstl1 expression during skeletal muscle differentiation of fibroblasts converted by MyoD. miRNA target site reporter assay, MyoD-driven fibroblast-to-muscle conversion, Northern blot The Journal of cell biology High 17030984
2011 Fstl1 directly binds BMP4 and negatively regulates BMP4/Smad1/5/8 signaling; genetic rescue with the BMP antagonist Noggin rescues pulmonary atelectasis in Fstl1-deficient mice, placing Fstl1 upstream of BMP4 signaling in lung development. Fstl1 knockout mouse, co-immunoprecipitation of Fstl1 with BMP4, Noggin epistasis rescue, pSmad1/5/8 signaling readout in vivo and in vitro Proceedings of the National Academy of Sciences of the United States of America High 21482757
2013 TGF-β signaling downregulates KSRP, switching a shared transcript from producing miR-198 to producing FSTL1 protein; FSTL1 promotes keratinocyte migration during wound re-epithelialization, while miR-198 inhibits migration by targeting DIAPH1, PLAU, and LAMC2. Human ex vivo skin organ culture, TGF-β pathway manipulation, KSRP knockdown, luciferase reporter, migration assay Nature High 23395958
2010 DIP2A was identified as a novel FSTL1-binding receptor on the cell surface of endothelial cells; DIP2A knockdown reduced FSTL1 binding to cells, abrogated FSTL1-stimulated survival, migration, network formation, and Akt phosphorylation in endothelial cells, and reduced FSTL1 cardioprotection in cardiac myocytes. Membrane fraction pull-down from endothelial cells, co-immunoprecipitation, siRNA knockdown of DIP2A, cell surface binding assay, functional endothelial and cardiomyocyte assays The Journal of biological chemistry High 20054002
2017 FSTL1 promotes EMT and airway remodeling by activating autophagy; inhibition of autophagy by LY-294002 or siRNA-ATG5 reduced FSTL1-induced EMT markers (E-cadherin, N-cadherin, vimentin) in bronchial epithelial cells. OVA-challenged mouse model, Fstl1 heterozygous mice, siRNA-ATG5 and pharmacological autophagy inhibition, TEM for autophagosomes, Western blot American journal of physiology. Lung cellular and molecular physiology Medium 28473327
2017 EGF sustains FSTL1 translation while suppressing miR-198, driving metastasis through dual pathways: FSTL1 blocks Wnt7a-mediated repression of ERK phosphorylation enabling MMP9 production; simultaneously, DIAPH1 (miR-198 target) sequesters Arpin to enhance directional migration via Arp2/3. HNSCC cell lines, luciferase reporter, FSTL1/DIAPH1 knockdown, ERK phosphorylation assay, MMP9 secretion, Arpin interaction The Journal of experimental medicine Medium 28827448
2018 Fstl1 binds DIP2A to block its nuclear translocation, preventing DIP2A from forming a complex with HDAC2-DMAP1; this increases H3K9 acetylation at the MGMT promoter and upregulates MGMT transcription, causing temozolomide resistance in glioblastoma. Co-immunoprecipitation of Fstl1 with DIP2A, chromatin immunoprecipitation (H3K9Ac at MGMT promoter), DIP2A knockdown epistasis, subcellular fractionation, in vivo xenograft Oncogene High 30542120
2012 Fstl1 directly binds ALK6 (BMPR1B) expressed on ureteric epithelial cells and antagonizes BMP signaling (elevated pSmad1/5/8 in Fstl1-null ureters), regulating ureteric epithelial cell proliferation and ureter development. Fstl1 knockout mouse, direct binding assay (Fstl1 to ALK6), pSmad1/5/8 immunostaining, histological analysis PloS one Medium 22485132
2017 TGF-β1 regulates Fstl1 expression at both transcriptional and translational levels through the Smad3-c-Jun pathway; the Smad2/3 pathway is required (inhibition abolishes TGF-β1-induced Fstl1), and a functional c-Jun transcription factor binding site in the Fstl1 promoter was identified by luciferase reporter analysis. Luciferase reporter assay with Fstl1 promoter, pathway inhibitor screen (Smad, MAPK, Akt), mouse pulmonary fibroblasts American journal of physiology. Lung cellular and molecular physiology Medium 28495857
2019 Crystal structure of the FK domain of murine Fstl1 was solved at high resolution, revealing that the FK domain forms a stable dimer in solution and in crystal; this domain is indispensable for Fstl1's function in TGF-β signaling transduction. X-ray crystallography, SEC-MALS for oligomeric state, FK domain deletion/mutation functional assay Protein science : a publication of the Protein Society High 31351024
2022 FSTL1 interacts with Wnt ligands (via its EC and VWC domains) and Frizzled receptors (FZD4, via EC domain) but not LRP6 co-receptor, enhancing Wnt3a association with FZD4 and promoting Wnt/β-catenin signaling and fibrogenesis in obstructed kidneys. Co-immunoprecipitation, domain deletion mapping, Fstl1 overexpression/inhibition in vivo, TOP/FOP flash reporter, single-cell RNA-seq The Journal of biological chemistry High 35525270
2022 Macrophage-expressed FSTL1, through its FK domain, directly binds intracellular PKM2, promotes PKM2 phosphorylation and nuclear translocation, reduces PKM2 ubiquitination, enhances glycolysis, and increases M1 macrophage polarization to promote liver fibrosis. Myeloid-specific FSTL1 KO mice, Co-IP of FSTL1 with PKM2, PKM2 phosphorylation/ubiquitination assays, nuclear fractionation, pharmacological PKM2 activator rescue Gut High 35140065
2021 FSTL1 secreted by activated fibroblasts binds TLR4 on hepatocellular carcinoma cells, activating AKT/mTOR/4EBP1 signaling to promote HCC growth, metastasis, and tumor-initiating cell maintenance. Recombinant FSTL1 treatment, FSTL1 overexpression conditioned medium, TLR4 binding assay, AKT/mTOR pathway readout, patient-derived 3D organoids, preclinical mouse model with FSTL1 blockade Cancer research Medium 34551961
2020 Dynamic resistance exercise stimulates skeletal muscle FSTL1 secretion; FSTL1 binds DIP2A receptor on endothelial cells and activates Smad2/3 signaling (independent of TGFβR1) to induce VEGF-A expression and promote cardiac angiogenesis post-myocardial infarction. AAV-FSTL1 injection, TGFβR1 inhibitor, DIP2A immunofluorescence, pSmad2/3 Western blot, HUVEC tube formation assay, rat MI model Journal of sport and health science Medium 33246164
2017 Fstl1 competitively binds BMP4 but not BMPR2, inhibiting BMP4-BMPR2 association and suppressing BMP4/Smad1/5/8 pathway activation, thereby promoting glioma cell proliferation. Co-immunoprecipitation of Fstl1 with BMP4 and BMPR2, BMP4 overexpression rescue, pSmad1/5/8 readout, orthotopic xenograft Cellular physiology and biochemistry Medium 29212066
2018 FSTL1 promotes CRC metastasis through activation of focal adhesion signaling and cytoskeleton rearrangement; FSTL1 interacts with VIM (vimentin) as identified by co-immunoprecipitation, and TGFβ1 induces FSTL1 expression via Smad3 transcription factor. Co-immunoprecipitation of FSTL1 with VIM, Smad3 transcription factor reporter, FSTL1 knockdown/overexpression migration/invasion assays, focal adhesion pathway readout Cell death & disease Medium 29844309
2017 FSTL1 promotes ESCC oncogenesis via NFκB-BMP signaling cross-talk; functional rescue experiments with NFκB and TLR4 inhibitors established pathway interdependence. FSTL1 shRNA and neutralizing antibody, mRNA profiling, NFκB/TLR4 inhibitor functional rescue, in vivo metastasis model Cancer research Medium 28883005
2017 Deletion of Fstl1 from the endocardial/endothelial lineage (Tie2-Cre) leads to sustained BMP and TGFβ signaling, ongoing EndMT and proliferation, causing myxomatous mitral valve disease, heart failure, and death, establishing Fstl1 as a negative regulator of BMP/TGFβ signaling in the endocardium. Conditional Tie2-Cre knockout, histology, echocardiography, BMP/TGFβ pathway immunostaining Arteriosclerosis, thrombosis, and vascular biology Medium 28705792
2020 Recombinant FSTL1 treatment of macrophages attenuates NF-κB p65 phosphorylation in an Nr4a1-dependent manner, placing Fstl1 upstream of Nr4a1-mediated NF-κB suppression in lung macrophages; FSTL1 hypomorphic mice develop spontaneous emphysema with dysregulated Nr4a1 expression. RNA sequencing, recombinant FSTL1 macrophage treatment, Nr4a1-dependent NF-κB p65 phosphorylation assay, FSTL1 hypomorphic mouse lung morphometry American journal of respiratory and critical care medicine Medium 31834999
2023 Skeletal muscle IRF4 transcriptionally regulates FSTL1 (confirmed by dual-luciferase assay); muscle-secreted FSTL1 acts on liver cells via distinct receptors (DIP2A and CD14) in different liver cell types to promote NASH pathology. Muscle-specific IRF4 KO mice, dual-luciferase reporter for FSTL1 promoter, proteomics, muscle FSTL1 re-expression rescue, co-culture experiments Nature communications High 37770480
2017 Fstl1 deletion in mice causes loss of myocardin/SRF transcription factors and impaired differentiation of airway smooth muscle cells, establishing Fstl1 as a regulator of smooth muscle cell differentiation in lung airway development. Fstl1 knockout mice, lacZ reporter for expression localization, histology, myocardin/SRF Western blot PloS one Medium 28574994
2020 FSTL1 promotes chondrocyte apoptosis via activation of the SAPK/JNK/Caspase3 signaling pathway; caspase-3 inhibitor Ac-DEVD-FMK impaired FSTL1-induced apoptosis. FSTL1 overexpression in human chondrocytes, flow cytometry apoptosis assay, Western blot for SAPK/JNK/Caspase3, pharmacological inhibitor rescue Gene Medium 31927008
2023 H2S stabilizes FSTL1 transcript via HuR (RNA-binding protein); FSTL1 activates Src kinase to open endothelial intercellular junctions (decreasing VE-cadherin, occludin, claudin-5, connexin-43), initiating angiogenesis independently of VEGFR2. siRNA knockdown of HuR, Src inhibitor vs. VEGFR2 inhibitor comparison, immunostaining of junction proteins, HUVEC permeability assay, hindlimb ischemia mouse model American journal of physiology. Cell physiology Medium 37694287
2023 FSTL1 promotes alveolar epithelial cell senescence through TGF-β1 signaling in a SENP1-dependent manner; FSTL1 upregulates SENP1 expression, and SENP1 mediates deSUMOylation of Smad4 and Ras to enhance TGF-β pathway activation; SENP1 knockdown blocked FSTL1-enhanced senescence and pulmonary fibrosis. FSTL1 overexpression in AECs, SENP1 siRNA knockdown, TGF-β signaling pathway assay, mouse pulmonary fibrosis model Cell biology international Medium 37369969

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 MyoD inhibits Fstl1 and Utrn expression by inducing transcription of miR-206. The Journal of cell biology 270 17030984
2022 FSTL1 promotes liver fibrosis by reprogramming macrophage function through modulating the intracellular function of PKM2. Gut 191 35140065
2011 Follistatin-like 1 (Fstl1) is a bone morphogenetic protein (BMP) 4 signaling antagonist in controlling mouse lung development. Proceedings of the National Academy of Sciences of the United States of America 190 21482757
2013 'See-saw' expression of microRNA-198 and FSTL1 from a single transcript in wound healing. Nature 181 23395958
2018 Long noncoding RNA OCC-1 suppresses cell growth through destabilizing HuR protein in colorectal cancer. Nucleic acids research 160 29931370
2004 Members of the Wnt, Fz, and Frp gene families expressed in postnatal mouse cerebral cortex. The Journal of comparative neurology 129 15116386
2010 DIP2A functions as a FSTL1 receptor. The Journal of biological chemistry 110 20054002
2017 Autophagy plays a role in FSTL1-induced epithelial mesenchymal transition and airway remodeling in asthma. American journal of physiology. Lung cellular and molecular physiology 93 28473327
2018 FSTL1 enhances chemoresistance and maintains stemness in breast cancer cells via integrin β3/Wnt signaling under miR-137 regulation. Cancer biology & therapy 86 30336071
2013 Crystal structure of the FRP and identification of the active site for modulation of OCP-mediated photoprotection in cyanobacteria. Proceedings of the National Academy of Sciences of the United States of America 82 23716688
2021 FSTL1 Secreted by Activated Fibroblasts Promotes Hepatocellular Carcinoma Metastasis and Stemness. Cancer research 81 34551961
1994 Molecular and biological characterization of fusion regulatory proteins (FRPs): anti-FRP mAbs induced HIV-mediated cell fusion via an integrin system. The EMBO journal 79 8187758
2004 Ameliorative effects of follistatin-related protein/TSC-36/FSTL1 on joint inflammation in a mouse model of arthritis. Arthritis and rheumatism 73 14872511
2018 FSTL1 interacts with VIM and promotes colorectal cancer metastasis via activating the focal adhesion signalling pathway. Cell death & disease 68 29844309
2013 Targeting FSTL1 prevents tumor bone metastasis and consequent immune dysfunction. Cancer research 68 23966294
2011 FSTL1 promotes arthritis in mice by enhancing inflammatory cytokine/chemokine expression. Arthritis and rheumatism 67 22006268
2020 Dynamic resistance exercise increases skeletal muscle-derived FSTL1 inducing cardiac angiogenesis via DIP2A-Smad2/3 in rats following myocardial infarction. Journal of sport and health science 65 33246164
2000 Regulation of a multigenic invasion programme by the transcription factor, AP-1: re-expression of a down-regulated gene, TSC-36, inhibits invasion. Oncogene 63 11103936
2007 The diacylated lipopeptide FSL-1 enhances phagocytosis of bacteria by macrophages through a Toll-like receptor 2-mediated signalling pathway. FEMS immunology and medical microbiology 62 17316370
2000 Expression of a TGF-beta1 inducible gene, TSC-36, causes growth inhibition in human lung cancer cell lines. Cancer letters 62 10814877
2014 The TLR2 ligand FSL-1 and the TLR5 ligand Flagellin mediate pro-inflammatory and pro-labour response via MyD88/TRAF6/NF-κB-dependent signalling. American journal of reproductive immunology (New York, N.Y. : 1989) 61 24635133
2017 FSTL1 Promotes Metastasis and Chemoresistance in Esophageal Squamous Cell Carcinoma through NFκB-BMP Signaling Cross-talk. Cancer research 59 28883005
1994 Characterization of a rat C6 glioma-secreted follistatin-related protein (FRP). Cloning and sequence of the human homologue. European journal of biochemistry 58 7957230
2017 EGF hijacks miR-198/FSTL1 wound-healing switch and steers a two-pronged pathway toward metastasis. The Journal of experimental medicine 57 28827448
2016 FSTL1 as a Potential Mediator of Exercise-Induced Cardioprotection in Post-Myocardial Infarction Rats. Scientific reports 57 27561749
2016 The purple Trp288Ala mutant of Synechocystis OCP persistently quenches phycobilisome fluorescence and tightly interacts with FRP. Biochimica et biophysica acta. Bioenergetics 54 27755972
2010 Downregulated expression of the secreted glycoprotein follistatin-like 1 (Fstl1) is a robust hallmark of preadipocyte to adipocyte conversion. Mechanisms of development 54 20043993
2018 Acute and Chronic Increases of Circulating FSTL1 Normalize Energy Substrate Metabolism in Pacing-Induced Heart Failure. Circulation. Heart failure 53 29317401
2017 TLR-4/miRNA-32-5p/FSTL1 signaling regulates mycobacterial survival and inflammatory responses in Mycobacterium tuberculosis-infected macrophages. Experimental cell research 53 28215633
2016 Knockdown of FSTL1 inhibits oxLDL-induced inflammation responses through the TLR4/MyD88/NF-κB and MAPK pathway. Biochemical and biophysical research communications 51 27569284
2006 The diacylated lipopeptide FSL-1 induces TLR2-mediated Th2 responses. FEMS immunology and medical microbiology 46 16965351
2018 Fstl1/DIP2A/MGMT signaling pathway plays important roles in temozolomide resistance in glioblastoma. Oncogene 45 30542120
2021 Downregulation of lncRNA SNHG14 attenuates osteoarthritis by inhibiting FSTL-1 mediated NLRP3 and TLR4/NF-κB pathway through miR-124-3p. Life sciences 44 33539913
1997 Decrease in the expression of a novel TGF beta1-inducible and ras-recision gene, TSC-36, in human cancer cells. Cancer letters 44 9065824
2020 Targeting FSTL1 for Multiple Fibrotic and Systemic Autoimmune Diseases. Molecular therapy : the journal of the American Society of Gene Therapy 43 33007201
2020 Circular RNA hsa_circ_0004812 impairs IFN-induced immune response by sponging miR-1287-5p to regulate FSTL1 in chronic hepatitis B. Virology journal 41 32188476
2017 TGF-β1 induces Fstl1 via the Smad3-c-Jun pathway in lung fibroblasts. American journal of physiology. Lung cellular and molecular physiology 40 28495857
2012 Fstl1 antagonizes BMP signaling and regulates ureter development. PloS one 39 22485132
2005 TSC-36/FRP inhibits vascular smooth muscle cell proliferation and migration. Experimental and molecular pathology 38 16256108
2018 OCP-FRP protein complex topologies suggest a mechanism for controlling high light tolerance in cyanobacteria. Nature communications 36 30250028
2018 Blocking the FSTL1-DIP2A Axis Improves Anti-tumor Immunity. Cell reports 35 30110636
2021 Inhibition of long non-coding RNA HOXA11-AS against neuroinflammation in Parkinson's disease model via targeting miR-124-3p mediated FSTL1/NF-κB axis. Aging 34 33839699
2020 Molecular functions of FSTL1 in the osteoarthritis. International immunopharmacology 33 32259701
2021 FSTL1-USP10-Notch1 Signaling Axis Protects Against Cardiac Dysfunction Through Inhibition of Myocardial Fibrosis in Diabetic Mice. Frontiers in cell and developmental biology 32 34957094
2017 Deletion of the short N-terminal extension in OCP reveals the main site for FRP binding. FEBS letters 31 28504309
2023 Metabolic crosstalk between skeletal muscle cells and liver through IRF4-FSTL1 in nonalcoholic steatohepatitis. Nature communications 30 37770480
2017 Fstl1 Promotes Glioma Growth Through the BMP4/Smad1/5/8 Signaling Pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 30 29212066
2002 Signaling pathways induced by lipoproteins derived from Mycoplasma salivarium and a synthetic lipopeptide (FSL-1) in normal human gingival fibroblasts. Microbiology and immunology 29 12008923
2022 Blocking FSTL1 boosts NK immunity in treatment of osteosarcoma. Cancer letters 28 35439537
2021 Circular RNA circ_HECTD1 regulates cell injury after cerebral infarction by miR-27a-3p/FSTL1 axis. Cell cycle (Georgetown, Tex.) 28 33843447
2005 Activity-dependent expression of occ1 in excitatory neurons is a characteristic feature of the primate visual cortex. Cerebral cortex (New York, N.Y. : 1991) 28 16151175
2022 Knockdown of FSTL1 inhibits microglia activation and alleviates depressive-like symptoms through modulating TLR4/MyD88/NF-κB pathway in CUMS mice. Experimental neurology 27 35367454
2017 Deletion of Fstl1 (Follistatin-Like 1) From the Endocardial/Endothelial Lineage Causes Mitral Valve Disease. Arteriosclerosis, thrombosis, and vascular biology 26 28705792
2017 FSTL1 suppresses tumor cell proliferation, invasion and survival in non-small cell lung cancer. Oncology reports 26 29115636
2017 The Toll-Like Receptor 2/6 Agonist, FSL-1 Lipopeptide, Therapeutically Mitigates Acute Radiation Syndrome. Scientific reports 25 29230065
2022 Follistatin-like 1 (FSTL1) interacts with Wnt ligands and Frizzled receptors to enhance Wnt/β-catenin signaling in obstructed kidneys in vivo. The Journal of biological chemistry 24 35525270
2021 FSTL1 aggravates OVA-induced inflammatory responses by activating the NLRP3/IL-1β signaling pathway in mice and macrophages. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 24 34076707
2017 The cyanobacterial Fluorescence Recovery Protein has two distinct activities: Orange Carotenoid Protein amino acids involved in FRP interaction. Biochimica et biophysica acta. Bioenergetics 23 28188781
2009 FSL-1, a bacterial-derived toll-like receptor 2/6 agonist, enhances resistance to experimental HSV-2 infection. Virology journal 23 19903337
2006 The synthetic analogue of mycoplasmal lipoprotein FSL-1 induces dendritic cell maturation through Toll-like receptor 2. FEMS immunology and medical microbiology 23 16420600
1984 Rutin-induced beta-glucosidase activity in Streptococcus faecium VGH-1 and Streptococcus sp. strain FRP-17 isolated from human feces: formation of the mutagen, quercetin, from rutin. Applied and environmental microbiology 23 6424566
2017 Knockdown of Fstl1 attenuates hepatic stellate cell activation through the TGF‑β1/Smad3 signaling pathway. Molecular medicine reports 22 28901425
2016 Alternative splicing of the OCC-1 gene generates three splice variants and a novel exonic microRNA, which regulate the Wnt signaling pathway. RNA (New York, N.Y.) 22 27986894
2015 Effect of the synthetic Toll-like receptor ligands LPS, Pam3CSK4, HKLM and FSL-1 in the function of bovine polymorphonuclear neutrophils. Developmental and comparative immunology 22 26026246
2017 Effects of FSTL1 on the proliferation and motility of breast cancer cells and vascular endothelial cells. Thoracic cancer 21 28857515
2020 Hsa_circ_0011290 regulates proliferation, apoptosis and glycolytic phenotype in papillary thyroid cancer via miR-1252/ FSTL1 signal pathway. Archives of biochemistry and biophysics 20 32234499
2019 FSTL1 Promotes Inflammatory Reaction and Cartilage Catabolism through Interplay with NFκB Signaling Pathways in an In Vitro ONFH Model. Inflammation 20 31011927
2021 FSTL1 increases cisplatin sensitivity in epithelial ovarian cancer cells by inhibition of NF-κB pathway. Cancer chemotherapy and pharmacology 19 33392640
2021 FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy. BMC pulmonary medicine 19 33509151
2020 MiR-524-5p Suppresses Migration, Invasion, and EMT Progression in Breast Cancer Cells Through Targeting FSTL1. Cancer biotherapy & radiopharmaceuticals 19 32298609
2021 Follistatin-Like-1 (FSTL1) Is a Fibroblast-Derived Growth Factor That Contributes to Progression of Chronic Kidney Disease. International journal of molecular sciences 18 34502419
2020 FSTL-1 Attenuation Causes Spontaneous Smoke-Resistant Pulmonary Emphysema. American journal of respiratory and critical care medicine 18 31834999
2019 Structural and functional study of FK domain of Fstl1. Protein science : a publication of the Protein Society 18 31351024
2019 Downregulation of FSTL‑1 attenuates the inflammation injury during Streptococcus pneumoniae infection by inhibiting the NLRP3 and TLR4/NF‑κB signaling pathway. Molecular medicine reports 18 31638229
2008 Differential expression patterns of occ1-related genes in adult monkey visual cortex. Cerebral cortex (New York, N.Y. : 1991) 18 19073625
2022 FSTL1-knockdown improves neural oscillation via decreasing neuronal-inflammation regulating apoptosis in Aβ1-42 induced AD model mice. Experimental neurology 17 36162512
2017 Follistatin like-1 (Fstl1) is required for the normal formation of lung airway and vascular smooth muscle at birth. PloS one 17 28574994
2014 FSL-1, a Toll-like Receptor 2/6 Agonist, Induces Expression of Interleukin-1α in the Presence of 27-hydroxycholesterol. The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 17 25598661
2021 Baicalin attenuates LPS-induced alveolar type II epithelial cell A549 injury by attenuation of the FSTL1 signaling pathway via increasing miR-200b-3p expression. Innate immunity 16 34000873
2020 Sulforaphene inhibits the progression of osteosarcoma via regulating FSTL1/NF-κB pathway. Life sciences 16 33017573
2016 A holistic approach to dissecting SPARC family protein complexity reveals FSTL-1 as an inhibitor of pancreatic cancer cell growth. Scientific reports 16 27886258
2024 FSTL1 Accelerates Nucleus Pulposus Cell Senescence and Intervertebral Disc Degeneration Through TLR4/NF-κB Pathway. Inflammation 15 38316670
2022 Ensemble Tree-Based Approach towards Flexural Strength Prediction of FRP Reinforced Concrete Beams. Polymers 15 35406177
2021 The lncRNA PVT1/miR-590-5p/FSTL1 axis modulates the proliferation and migration of airway smooth muscle cells in asthma. Autoimmunity 15 33825599
2021 Circ_0001490/miR-579-3p/FSTL1 axis modulates the survival of mycobacteria and the viability, apoptosis and inflammatory response in Mycobacterium tuberculosis-infected macrophages. Tuberculosis (Edinburgh, Scotland) 15 34555658
2020 FSTL1 promotes nitric oxide-induced chondrocyte apoptosis via activating the SAPK/JNK/caspase3 signaling pathway. Gene 15 31927008
2017 The Correlation between FSTL1 Expression and Airway Remodeling in Asthmatics. Mediators of inflammation 15 28845090
2004 Follistatin-related protein gene (FRP) is expressed in the synovial tissues of rheumatoid arthritis, but its polymorphisms are not associated with genetic susceptibility. Clinical and experimental rheumatology 15 15638044
2023 FSTL1 promotes alveolar epithelial cell aging and worsens pulmonary fibrosis by affecting SENP1-mediated DeSUMOylation. Cell biology international 14 37369969
2023 The TLR2/TLR6 ligand FSL-1 mitigates radiation-induced hematopoietic injury in mice and nonhuman primates. Proceedings of the National Academy of Sciences of the United States of America 14 38051771
2022 COL5A1 Promotes the Progression of Gastric Cancer by Acting as a ceRNA of miR-137-3p to Upregulate FSTL1 Expression. Cancers 14 35805015
2006 A pleiotropic regulator, Frp, affects exopolysaccharide synthesis, biofilm formation, and competence development in Streptococcus mutans. Infection and immunity 14 16861645
2024 FSTL1: A double-edged sword in cancer development. Gene 13 38346455
2021 ZFAS1 knockdown inhibits fibroblast-like synoviocyte proliferation, migration, invasion and inflammation, and promotes apoptosis via miR-3926/FSTL1 in rheumatoid arthritis. Experimental and therapeutic medicine 13 34306188
2017 Knockdown of FSTL1 inhibits PDGF‑BB‑induced human airway smooth muscle cell proliferation and migration. Molecular medicine reports 13 28393245
2023 Skeletal muscle-derived FSTL1 starting up angiogenesis by regulating endothelial junction via activating Src pathway can be upregulated by hydrogen sulfide. American journal of physiology. Cell physiology 12 37694287
2022 CircPTTG1IP knockdown suppresses rheumatoid arthritis progression by targeting miR-431-5p/FSTL1 axis. Transplant immunology 12 35933079
2021 Inhibition of microRNA-143-3p Attenuates Cerebral Ischemia/Reperfusion Injury by Targeting FSTL1. Neuromolecular medicine 12 33709299
2015 The role of oxidation in FSL-1 induced signaling pathways of an atopic dermatitis model in HaCaT keratinocytes. Advances in experimental medicine and biology 12 25510360
2000 Induction of c-Src in human blood monocytes by anti-CD98/FRP-1 mAb in an Sp1-dependent fashion. Cellular immunology 12 11069718