Affinage

CLCF1

Cardiotrophin-like cytokine factor 1 · UniProt Q9UBD9

Length
225 aa
Mass
25.2 kDa
Annotated
2026-06-09
39 papers in source corpus 22 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CLCF1 (NNT-1/BSF-3) is a secreted IL-6-family cytokine that signals through the tripartite CNTFR receptor complex to activate JAK-STAT (predominantly STAT3), MAPK, and PI3K/AKT pathways across many cell types (PMID:15450249). Efficient cellular secretion of CLCF1 depends on heteromeric complex formation with the soluble receptor CRLF1 (CLF-1) or soluble CNTFR, which act as obligate chaperones (PMID:15450249, PMID:40393625). Through CNTFR-driven STAT3 signaling CLCF1 exerts pleiotropic context-dependent effects: it transcriptionally suppresses PGC-1α/β to inhibit mitochondrial biogenesis and thermogenesis in brown adipocytes (PMID:37549287), remodels podocyte cytoskeleton and increases glomerular albumin permeability (PMID:26146641), and drives endothelial-to-mesenchymal transition in glomerular endothelial cells via JAK2/STAT3 (PMID:40731368). In bone, CLCF1 engages STAT1/IRF1 and interferon signaling to suppress both osteoblastogenesis (PMID:31248987) and osteoclastogenesis (PMID:34364014). As a tumor-promoting factor, CLCF1 is secreted by cancer-associated fibroblasts to stimulate lung tumor growth through CNTFR (PMID:22962265), and supports aerobic glycolysis and sorafenib resistance in hepatocellular carcinoma via PI3K/AKT (PMID:33097691); engineered soluble CNTFR decoy (eCNTFR-Fc) sequesters CLCF1, suppresses STAT3/TGF-β-driven tumor growth, and reshapes the immune microenvironment (PMID:31700175, PMID:42102942). CLCF1 also limits Th1 differentiation by binding IL12Rβ2 and promoting its proteasomal, ubiquitination-independent degradation (PMID:40628045), and provides neurotrophic and protective support in the CNS by promoting oligodendrocyte precursor and Müller glia responses (PMID:36334441, PMID:36846595).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2004 Medium

    Established CLCF1 as a functional CNTFR ligand and defined the requirement for chaperone-dependent secretion, answering how this cytokine reaches the extracellular space and which receptor it engages.

    Evidence Receptor binding, signal transduction, and co-expression secretion assays in cell lines

    PMID:15450249

    Open questions at the time
    • Structural basis of CLCF1-CRLF1/sCNTFR complex not resolved
    • Relative physiological contributions of CRLF1 vs sCNTFR chaperones unclear
  2. 2012 Medium

    Showed CLCF1-CNTFR is a paracrine tumor-growth signal from cancer-associated fibroblasts, framing the cytokine as a stromal driver of lung cancer.

    Evidence In vivo xenografts, expression analysis, and signaling inhibition in NSCLC

    PMID:22962265

    Open questions at the time
    • Downstream tumor-cell effectors not fully mapped
    • Generality across cancer types not addressed here
  3. 2015 High

    Demonstrated that CLCF1-driven STAT3 activation produces direct functional consequences in podocytes and glomerular permeability, linking the cytokine to renal filtration barrier biology.

    Evidence In vitro phosphorylation, podocyte morphology imaging, ex vivo glomeruli permeability, and in vivo albuminuria assays

    PMID:26146641

    Open questions at the time
    • Receptor complex stoichiometry on podocytes not defined
    • In vivo source of CLCF1 in disease unclear
  4. 2019 Medium

    Resolved CLCF1's role in bone homeostasis, showing it suppresses osteoblastogenesis through STAT1/STAT3 in mesenchymal stem cells.

    Evidence MSC differentiation, Western blot phosphorylation, and gene expression assays

    PMID:31248987

    Open questions at the time
    • Receptor identity on MSCs not confirmed
    • Balance between STAT1 and STAT3 contributions not dissected
  5. 2019 High

    Validated CLCF1-CNTFR as a druggable oncogenic axis using an engineered decoy receptor, with KRAS mutation status predicting response.

    Evidence Xenograft and GEM KRAS-mutant lung adenocarcinoma models with eCNTFR-Fc treatment

    PMID:31700175

    Open questions at the time
    • Mechanism linking KRAS GTPase mutations to CLCF1 dependence unresolved
  6. 2021 High

    Defined a STAT1/IRF1 interferon-driven mechanism by which CLCF1 suppresses osteoclast differentiation, complementing its osteoblast effects.

    Evidence RANKL differentiation, dentine resorption, ovariectomized/calvarial models, and STAT1 blockade rescue

    PMID:34364014

    Open questions at the time
    • How CLCF1 biases toward STAT1 vs STAT3 in different cells not explained
  7. 2023 High

    Established a CNTFR→STAT3→PGC-1α/β transcriptional axis through which CLCF1 suppresses brown adipose thermogenesis and energy expenditure.

    Evidence Adipocyte-specific transgenic mice, CNTFR/STAT3 inhibition, transcriptional and mitochondrial assays

    PMID:37549287

    Open questions at the time
    • Endogenous regulation of adipose CLCF1 not defined
    • Relevance to human metabolic disease untested
  8. 2020 Medium

    Connected CLCF1 to cancer metabolism and drug resistance, showing miR-30a-5p-controlled CLCF1 drives aerobic glycolysis via PI3K/AKT in sorafenib-resistant HCC.

    Evidence Luciferase reporter, ECAR glycolysis assay, Western blot, and xenografts

    PMID:33097691

    Open questions at the time
    • Receptor engagement in this autocrine setting not confirmed
    • Direct glycolytic gene targets only partially mapped
  9. 2018 High

    Revealed that lipoprotein and ApoE association modulates CLCF1 activity, providing a mechanism for extracellular regulation of its signaling.

    Evidence Co-IP, proximity ligation, FPLC fractionation, ligand blot, STAT3 assays, and oxygen-induced retinopathy model

    PMID:29507344

    Open questions at the time
    • Physiological trigger of lipoprotein association unknown
    • Structural binding interface with ApoE/VLDL undefined
  10. 2025 Medium

    Identified a non-canonical immunoregulatory mechanism: CLCF1 binds IL12Rβ2 and drives its proteasomal degradation to restrain Th1 differentiation.

    Evidence Hematopoietic Clcf1 knockout mice, T cell IFNγ measurement, co-IP, and proteasome inhibitor rescue

    PMID:40628045

    Open questions at the time
    • Ubiquitination-independent degradation route not molecularly defined
    • Whether this is CNTFR-independent not fully established
  11. 2025 Medium

    Extended CLCF1 transcriptional control and pathology, identifying MAFF/BACH1 as direct promoter activators and CLCF1-STAT3 as hepatoprotective in ischemia-reperfusion injury.

    Evidence CUT&Tag, RNA-seq, and adenoviral MAFF manipulation in mouse IRI

    PMID:40169936

    Open questions at the time
    • Generality of MAFF/BACH1 regulation beyond liver unknown
  12. 2025 Medium

    Demonstrated CRLF1/CLCF1 heterodimer JAK/STAT3 signaling drives senescence and SASP in nucleus pulposus cells, implicating the axis in disc degeneration.

    Evidence Co-IP, fluorescence colocalization, RNA-seq, and in vivo rat disc degeneration model

    PMID:39986601

    Open questions at the time
    • Relative roles of CRLF1 vs CLCF1 in signaling output not separated
  13. 2026 Medium

    Uncovered a hepatic CLCF1-CNTFR pathway that reshapes bile acid metabolism and gut microbiota to protect against cholestasis, broadening CLCF1's metabolic roles.

    Evidence Hepatocyte-specific Cntfr knockout, AAV Clcf1 overexpression, bile acid profiling, FXR-FGF15 measurement, and microbiome analysis

    PMID:41840139

    Open questions at the time
    • Direct transcriptional targets controlling bile acid enzymes not identified
    • Mechanism of FXR-SHP independence unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CLCF1 selects between STAT3, STAT1, and proteasomal (IL12Rβ2) outputs across tissues, and the structural basis of its receptor and chaperone complexes, remain unresolved.
  • No structural model of the CLCF1-CNTFR-gp130-LIFR complex in the corpus
  • Determinants of cell-type-specific STAT bias unknown
  • Mechanism of CNTFR-independent signaling not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0098772 molecular function regulator activity 1
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3
Partners
APOECNTFRCRLF1GP130IL12RB2LIFR
Complex memberships
CLCF1-CRLF1 heterodimerCLCF1-sCNTFR complexCNTFR/gp130/LIFR receptor complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 CLCF1 (NNT-1/BSF-3) is a second ligand for the tripartite CNTFR receptor complex and activates JAK-STAT, MAPK, and PI3K/Akt signaling pathways in various cell systems. Receptor binding and signal transduction assays in cell lines Cytokine & growth factor reviews Medium 15450249
2004 Cellular secretion of CLCF1 requires heteromeric complex formation with either cytokine-like factor-1 (CLF-1/CRLF1) or soluble CNTFR (sCNTFR) as chaperone partners. Co-expression and secretion assays Cytokine & growth factor reviews Medium 15450249
1999 NR6 (CLCF1 alias used for the soluble haemopoietin receptor; however this paper describes the soluble receptor CRLF1/NR6, not CLCF1 itself) — NOTE: This paper describes the receptor NR6, which is CRLF1, not CLCF1 directly. EXCLUDED from CLCF1 discoveries. N/A N/A Low 10359701
2012 CLCF1-CNTFR signaling promotes growth of non-small cell lung cancer cells in vivo; CLCF1 is secreted by cancer-associated fibroblasts and directly stimulates tumor cell growth. In vivo xenograft studies, gene expression analysis, functional studies with CLCF1-CNTFR signaling inhibition Cancer research Medium 22962265
2015 CLCF1 activates JAK/STAT3 phosphorylation in multiple cell types including podocytes, activates podocyte cytoskeletal remodeling (lamellipodia formation and loss of stress fibers), and increases glomerular albumin permeability in isolated rat glomeruli. In vitro phosphorylation assays, podocyte morphology imaging, isolated rat glomeruli permeability assay, in vivo injection with urinary albumin measurement Journal of immunology research High 26146641
2019 A high-affinity engineered soluble CNTFR decoy receptor (eCNTFR-Fc) sequesters CLCF1 and inhibits its oncogenic CNTFR signaling, suppressing tumor growth in xenograft and autochthonous KRAS-mutant lung adenocarcinoma mouse models; effectiveness correlated with KRAS GTPase-retaining mutations. Xenograft and GEM mouse models, eCNTFR-Fc treatment, correlation with KRAS mutation status Nature medicine High 31700175
2019 CLCF1 binds mouse mesenchymal stem cells (MSCs), triggers STAT1 and STAT3 phosphorylation, inhibits upregulation of master osteogenesis genes, and prevents osteoblast generation and mineralization. In vitro MSC differentiation assay, phosphorylation assays (Western blot), gene expression analysis The Journal of biological chemistry Medium 31248987
2020 miR-30a-5p directly targets the CLCF1 3'UTR, suppressing CLCF1 expression; sorafenib-mediated suppression of miR-30a-5p leads to CLCF1 upregulation, which promotes aerobic glycolysis via PI3K/AKT signaling and downstream glycolytic gene activation in sorafenib-resistant HCC cells. Dual luciferase reporter assay (miR-30a-5p targeting CLCF1), ECAR glycolysis assay, Western blot for PI3K/AKT pathway, xenograft mouse model Cell death & disease Medium 33097691
2021 CLCF1 suppresses osteoclast differentiation by activating interferon signaling (STAT1 and IRF1 in macrophages) and suppressing NF-κB signaling; STAT1 blockade in macrophages abolished CLCF1's inhibitory effect on osteoclastogenesis in vitro. RANKL-stimulated monocyte differentiation assay, dentine slice resorption assay, ovariectomized and calvarial mouse models, Western blot for STAT1/IRF1, STAT1 blockade rescue experiment Bone High 34364014
2023 CLCF1 binds and activates CNTFR, augmenting STAT3 signaling, which transcriptionally inhibits PGC-1α and PGC-1β, thereby suppressing mitochondrial biogenesis and thermogenesis in brown adipocytes; adipocyte-specific CLCF1 transgenic mice show impaired energy expenditure and cold intolerance. Adipocyte-specific transgenic mouse model, CNTFR/STAT3 inhibition experiments, ChIP or transcriptional reporter for PGC-1α/1β, mitochondrial biogenesis assays Proceedings of the National Academy of Sciences of the United States of America High 37549287
2018 CLCF1 forms complexes with all three major isoforms of ApoE (co-immunoprecipitation and proximity assays) and co-purifies with plasma lipoproteins (VLDL and LDL) in mouse and human serum; CLCF1 complexed with VLDL shows significantly reduced STAT3 phosphorylation activity, and VLDL abrogates CLCF1's anti-angiogenic effects in an oxygen-induced retinopathy mouse model. Co-immunoprecipitation, proximity ligation assay, FPLC fractionation of serum, ligand blot assay, STAT3 phosphorylation assay, oxygen-induced retinopathy mouse model Scientific reports High 29507344
2022 CNTF stimulation of astrocytes induces Clcf1 expression; secreted Clcf1 from astrocytes promotes differentiation of oligodendrocyte precursor cells (OPCs), and this effect is blocked by a Clcf1 antibody. Cell culture stimulation assay, antibody neutralization experiment, differentiation assay Biochemical and biophysical research communications Medium 36334441
2023 Clcf1 and Crlf1a are expressed in Müller glia of the light-damaged zebrafish retina; intravitreal CLCF1/CRLF1 injection protects rod photoreceptors from cell death and induces rod precursor cell proliferation; CNTFR, Clcf1, and Crlf1a are required for Müller glia proliferation after light damage. Zebrafish light-damage retina model, morpholino/genetic knockdown of Clcf1/Crlf1a/CNTFR, intravitreal injection of CLCF1/CRLF1 protein, cell proliferation and survival assays Frontiers in cell and developmental biology Medium 36846595
2025 The CRLF1/CLCF1 heterodimer (confirmed by fluorescence colocalization and co-immunoprecipitation) activates JAK/STAT3 signaling in nucleus pulposus cells, enhancing production of senescence-associated secretory phenotype (SASP) factors and accelerating cell senescence; CRLF1 knockdown reduces extracellular matrix degradation and NPC senescence in vitro and alleviates intervertebral disc degeneration in vivo. Co-immunoprecipitation, fluorescence colocalization, RNA-seq, in vitro NPC culture, in vivo rat disc degeneration model with pain behavior testing Osteoarthritis and cartilage Medium 39986601
2025 MAFF and BACH1 heterodimers directly bind the CLCF1 promoter (identified by CUT&Tag) and transcriptionally activate CLCF1 expression; elevated CLCF1 subsequently activates STAT3 signaling to reduce hepatocyte apoptosis and inflammation in hepatic ischemia-reperfusion injury. CUT&Tag chromatin profiling, RNA sequencing, adenoviral MAFF overexpression/knockdown in mouse IRI model Cellular & molecular biology letters Medium 40169936
2025 CLCF1 interacts physically with IL12Rβ2 and promotes its degradation through the proteasome in a ubiquitination-independent manner, thereby reducing IL12Rβ2 surface expression and limiting Th1 (IFNγ) differentiation; Clcf1 knockout in hematopoietic cells results in increased IFNγ production by CD4+ T cells upon IL-12 stimulation. Hematopoietic-specific Clcf1 knockout mouse (Vav-Cre), T cell IFNγ measurement, co-immunoprecipitation of CLCF1 and IL12Rβ2, proteasome inhibitor rescue experiments Cytokine Medium 40628045
2025 CLCF1 overexpression in high-glucose-stimulated glomerular endothelial cells activates JAK2/STAT3 signaling and promotes endothelial-to-mesenchymal transition (EndMT); CLCF1 knockdown attenuates HG-induced EndMT markers (α-SMA, vimentin), and re-activation of JAK2/STAT3 by colivelin rescues the phenotype in CLCF1-knockdown cells. siRNA knockdown and plasmid overexpression in HRGECs, Western blot for JAK2/STAT3 phosphorylation and EMT markers, colivelin rescue experiment European journal of medical research Medium 40731368
2025 CLCF1 regulates macrophage efferocytosis and modulates the NF-κB pathway in macrophages and microglia, controlling inflammation and promoting neuronal repair after CO poisoning; efferocytosis promotes M2 macrophage polarization (increased IL-10, reduced TNF-α and IL-1β). In vivo rat CO poisoning model, CLCF1 expression modulation, cytokine measurement, behavioral testing for cognitive outcomes Brain, behavior, and immunity Low 40081779
2024 eCNTFR-Fc blockade of CLCF1-CNTFR signaling shifts the tumor microenvironment from immunosuppressive to immunostimulatory macrophage phenotype and increases activated T, NKT, and NK cells; combination with anti-PD1 is more effective than single-agent therapy in syngeneic allograft and GEM lung adenocarcinoma models. Syngeneic allograft model, GEM lung adenocarcinoma model, eCNTFR-Fc treatment, immune cell phenotyping Research squarepreprint Medium 38562778
2026 Hepatic CLCF1 acting through CNTFR suppresses bile acid synthesis enzymes independently of FXR-SHP signaling, selectively enriches FXR-agonistic bile acids in the gut to activate the intestinal FXR-FGF15 axis, and remodels gut microbiota to favor Firmicutes; hepatocyte-specific CNTFR deletion worsens cholestasis, while AAV-mediated hepatic Clcf1 overexpression attenuates cholestatic injury in Mdr2-/- and DDC-fed mice. Hepatocyte-specific Cntfr knockout, AAV-mediated Clcf1 overexpression, bile acid profiling, intestinal FXR-FGF15 pathway measurement, gut microbiome analysis, gut-restricted FXR antagonism rescue Communications biology Medium 41840139
2026 eCNTFR-mediated blockade of CLCF1-CNTFR axis in HCC suppresses STAT3 signaling and TGF-β production in tumor cells, inhibiting tumor growth, stemness, and immunosuppressive TME formation; eCNTFR-armored GPC3 CAR-T cells show enhanced cytotoxicity and cytokine production. In vitro cytotoxicity assay, cytokine production measurement, xenograft mouse model, STAT3 and TGF-β signaling assays Pharmacological research Medium 42102942
2031 PRODUCTION NOTE: CLCF1 protein secretion requires co-expression with either CRLF1 or sCNTFR, which act as chaperones enabling CLCF1 to be secreted; CLCF1 alone is not secreted efficiently from mammalian expression systems. Transient co-expression in ExpiCHO-S and Expi293F cells, protein secretion measurement Protein expression and purification Medium 40393625
2003 CLCF1 (NNT-1/BSF-3) mRNA expression in pituitary folliculostellate cells is induced by PKC-, PKA-, and ERK1/2-dependent mechanisms downstream of PACAP and VIP receptor activation; dexamethasone inhibits PKC-stimulated CLCF1 expression. Northern blot, pharmacological inhibitors (H-7, GF109203X, H-89, U0126), phorbol ester and cAMP stimulation, RT-PCR receptor identification Endocrinology Medium 14605001

Source papers

Stage 0 corpus · 39 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1983 Platelet-derived growth factor stimulates Na+/H+ exchange and induces cytoplasmic alkalinization in NR6 cells. Proceedings of the National Academy of Sciences of the United States of America 156 6312448
2012 Cross-species functional analysis of cancer-associated fibroblasts identifies a critical role for CLCF1 and IL-6 in non-small cell lung cancer in vivo. Cancer research 119 22962265
2020 The miR-30a-5p/CLCF1 axis regulates sorafenib resistance and aerobic glycolysis in hepatocellular carcinoma. Cell death & disease 73 33097691
2015 Renal and Hematological Effects of CLCF-1, a B-Cell-Stimulating Cytokine of the IL-6 Family. Journal of immunology research 70 26146641
1999 Suckling defect in mice lacking the soluble haemopoietin receptor NR6. Current biology : CB 68 10359701
2019 Antitumor activity of an engineered decoy receptor targeting CLCF1-CNTFR signaling in lung adenocarcinoma. Nature medicine 63 31700175
1991 Enhanced tumorigenesis of NR6 cells which express non-down-regulating epidermal growth factor receptors. Cancer research 49 1933876
2022 CRLF1 and CLCF1 in Development, Health and Disease. International journal of molecular sciences 44 35055176
2015 Cardiotrophin-like cytokine factor 1 (CLCF1) and neuropoietin (NP) signalling and their roles in development, adulthood, cancer and degenerative disorders. Cytokine & growth factor reviews 42 26198769
1990 Nucleocytoplasmic transport is enhanced concomitant with nuclear accumulation of epidermal growth factor (EGF) binding activity in both 3T3-1 and EGF receptor reconstituted NR-6 fibroblasts. The Journal of cell biology 32 2307699
2004 Novel neurotrophin-1/B cell-stimulating factor-3 (NNT-1/BSF-3)/cardiotrophin-like cytokine (CLC)--a novel gp130 cytokine with pleiotropic functions. Cytokine & growth factor reviews 27 15450249
2010 Cold-induced sweating syndrome: CISS1 and CISS2: manifestations from infancy to adulthood. Four new cases. Journal of the neurological sciences 26 20400119
2023 CLCF1 signaling restrains thermogenesis and disrupts metabolic homeostasis by inhibiting mitochondrial biogenesis in brown adipocytes. Proceedings of the National Academy of Sciences of the United States of America 25 37549287
2019 Cardiotrophin-like cytokine (CLCF1) modulates mesenchymal stem cell osteoblastic differentiation. The Journal of biological chemistry 16 31248987
2021 Cardiotrophin Like Cytokine Factor 1 (CLCF1) alleviates bone loss in osteoporosis mouse models by suppressing osteoclast differentiation through activating interferon signaling and repressing the nuclear factor-κB signaling pathway. Bone 14 34364014
2023 Clcf1/Crlf1a-mediated signaling is neuroprotective and required for Müller glia proliferation in the light-damaged zebrafish retina. Frontiers in cell and developmental biology 13 36846595
2018 Effect of human very low-density lipoproteins on cardiotrophin-like cytokine factor 1 (CLCF1) activity. Scientific reports 12 29507344
1995 Ligand-induced translocation of epidermal growth factor receptor to the nucleus of NR6/HER fibroblasts is serum dependent. Experimental cell research 12 7698257
2003 Expression of novel neurotrophin-1/B-cell stimulating factor-3 (NNT-1/BSF-3) in murine pituitary folliculostellate TtT/GF cells: pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide-induced stimulation of NNT-1/BSF-3 is mediated by protein kinase A, protein kinase C, and extracellular-signal-regulated kinase1/2 pathways. Endocrinology 11 14605001
2025 CRLF1/CLCF1 heterodimer involvement in intervertebral disc degeneration via exacerbation of extracellular matrix degradation and nucleus pulposus cell senescence. Osteoarthritis and cartilage 9 39986601
2011 Expression of Bcl2l1, Clcf1, IL-28ra and Pias1 in the mouse heart after single and repeated administration of chlorpromazine. Legal medicine (Tokyo, Japan) 8 21683644
2025 MAFF alleviates hepatic ischemia-reperfusion injury by regulating the CLCF1/STAT3 signaling pathway. Cellular & molecular biology letters 7 40169936
2022 CLCF1 is up-regulated in renal ischemia reperfusion injury and may associate with FOXO3. Annals of translational medicine 7 35530960
2001 Diesel exhaust particle-induced cell death of human leukemic promyelocytic cells HL-60 and their variant cells HL-NR6. Biological & pharmaceutical bulletin 6 11305595
1993 Differential activity of the RVF enhancer element in the decreased expression of the neu oncogene in NR-6 cells versus parental Swiss Webster 3T3 cells. Molecular carcinogenesis 6 8094619
2024 The CLCF1-CNTFR axis drives an immunosuppressive tumor microenvironment and blockade enhances the effects of established cancer therapies. Research square 5 38562778
2022 CNTF induces Clcf1 in astrocytes to promote the differentiation of oligodendrocyte precursor cells. Biochemical and biophysical research communications 5 36334441
2025 Regulation of macrophage efferocytosis by the CLCF1/NF-κB pathway improves neurological and cognitive impairment following CO poisoning. Brain, behavior, and immunity 2 40081779
2025 High-yield production of recombinant CLCF1 protein fused with human serum albumin in animal cells and toxicity evaluation in rodents. Protein expression and purification 1 40393625
2025 CLCF1 promotes IL12Rβ2 proteolysis and limits Th1 differentiation. Cytokine 1 40628045
2025 CLCF1 contributes to high-glucose-induced EndMT by modulating JAK2/STAT3 signaling. European journal of medical research 1 40731368
2026 Integrating metabolomics, network pharmacology and molecular dynamics simulations reveals that Xiehuang San targets CLCF1-STAT3 to restore insulin signaling in T2DM. Journal of ethnopharmacology 0 41628867
2026 Insights into the regulation and signaling landscape of cardiotrophin-like cytokine factor 1 (CLCF1). Biochimica et biophysica acta. Molecular cell research 0 41662978
2026 The secretory protein, CLCF1, improves cholestatic liver disease by inhibiting hepatic bile acid synthesis and promoting bile acid excretion. Communications biology 0 41840139
2026 Saikosaponin D and paeoniflorin improve the HCC immune microenvironment via CLCF1/PD-L1 mediated crosstalk between CAFs and tumor cells. Scientific reports 0 41974852
2026 Blockade of the CLCF1-CNTFR axis enhances the efficacy of GPC3 CAR-T cell therapy in hepatocellular carcinoma. Pharmacological research 0 42102942
2025 CLCF1 Exercise-induced Myokine Protocol for Investigating RANKL/OPG Bone Protection Mechanisms in Postmenopausal Osteoporosis. Journal of visualized experiments : JoVE 0 41284622
2024 Reduced serum CLCF1 levels in hyperthyroidism patients and T3-treated mice. The Journal of endocrinology 0 38842921
2020 Crisponi syndrome/cold-induced sweating syndrome type 2: Reprogramming of CS/CISS2 individual derived fibroblasts into three clones of one iPSC line. Stem cell research 0 32512309

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