Affinage

SMAD7

SMAD family member 7 · UniProt O15105

Length
426 aa
Mass
46.4 kDa
Annotated
2026-06-10
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SMAD7 is an inhibitory Smad that serves as the central negative-feedback brake on TGF-β/BMP-family signaling: it is rapidly and directly induced by TGF-β1, activin, and BMP-7, and blocking it amplifies TGF-β responses (PMID:9712726). Mechanistically, SMAD7 associates with activated type I receptors to terminate signaling through two complementary routes — it acts as an adaptor that recruits the GADD34–PP1c holoenzyme (with SARA controlling PP1c localization) to dephosphorylate TβRI (PMID:14718519), and it recruits the E3 ligase SMURF2 to drive receptor turnover, an interaction gated by deubiquitination of SMAD7 at K220 by OTUD1, which exposes its PY motif (PMID:29235476). A crystal structure of the SMAD7 MH2 domain reveals a unique three-finger surface that rationalizes its broad inhibitory reach across TGF-β-family type I receptors (PMID:33166654). SMAD7 abundance is itself a regulatory node: p300-mediated acetylation and SMURF1-mediated ubiquitination compete at the same N-terminal lysines to set protein stability (PMID:12408818), with OTUD1 and USP26 stabilizing the protein (PMID:29235476, PMID:28381482) and HERC3 promoting its autolysosomal degradation (PMID:30862693). Its transcription is set by repressors including Ski/Smad4 at the SBE (PMID:15128733), HDAC5/MEF2A (PMID:36263180), and TIEG1 (PMID:28108300) at the promoter. Beyond receptor antagonism, SMAD7 has TGF-β-independent activities: a nuclear coactivator function that potentiates MyoD-driven myogenesis (PMID:16880533, PMID:19995910), direct binding to gp130 that amplifies LIF/STAT3 signaling to sustain pluripotency (potentiated by PRMT5 methylation of Arg-57) (PMID:28874583, PMID:34026434), recruitment of SMURF2 to β-catenin to suppress Wnt signaling (PMID:16950122), binding to ErbB2 to restrain fibrogenic signaling (PMID:34905511), and binding to IκBα to inhibit NF-κB (PMID:36739479). Functionally these activities converge on suppression of fibrosis (PMID:38899461, PMID:10393693), regulation of iron homeostasis through BMP–Smad control of hepcidin (PMID:29575577, PMID:20040761), cardiac development (PMID:18952608), and tissue differentiation programs (PMID:16950122, PMID:16880533).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 Medium

    Established SMAD7 as a TGF-β/BMP-induced negative feedback regulator rather than a signal transducer, defining the inhibitory-Smad concept.

    Evidence mRNA induction assays and antisense knockdown in cell lines; Xenopus animal cap and microinjection assays showing receptor association and neural induction

    PMID:9640328 PMID:9705232 PMID:9712726

    Open questions at the time
    • Did not resolve the biochemical mechanism of receptor inhibition
    • Stoichiometry and binding mode at type I receptors undefined
  2. 2002 High

    Defined how SMAD7 protein levels are set, showing acetylation and ubiquitination compete at shared N-terminal lysines to control stability.

    Evidence Co-IP, in vitro acetylation, lysine mutagenesis, and ubiquitination assays identifying p300 and SMURF1

    PMID:12408818

    Open questions at the time
    • Did not establish upstream signals controlling the acetylation/ubiquitination switch
    • Physiological stoichiometry of acetylation in vivo unaddressed
  3. 2004 High

    Resolved the catalytic mechanism of receptor shutdown, showing SMAD7 is an adaptor delivering a phosphatase to TβRI.

    Evidence Co-IP, RNAi epistasis, in vitro phosphatase assays with PP1 inhibitor, and SARA localization control

    PMID:14718519

    Open questions at the time
    • Relative contribution of dephosphorylation versus receptor degradation not quantified
    • Whether GADD34-PP1c recruitment operates on all type I receptors unknown
  4. 2004 High

    Identified transcriptional repression of SMAD7 as a tuning mechanism, with Ski/Smad4 acting at the SBE.

    Evidence Luciferase reporters, ChIP on the endogenous promoter, SBE mutagenesis, and Ski RNAi

    PMID:15128733

    Open questions at the time
    • Did not map combinatorial control with other promoter factors
    • Cell-type specificity of Ski repression unaddressed
  5. 2006 High

    Revealed TGF-β-independent nuclear and cytoplasmic functions, dissociating SMAD7 from pure receptor antagonism.

    Evidence Co-IP, siRNA, promoter transactivation, and transgenic/knockout mouse models for MyoD-driven myogenesis and β-catenin/SMURF2-mediated Wnt suppression

    PMID:16880533 PMID:16950122

    Open questions at the time
    • Whether nuclear functions require partial receptor pathway input not fully separated
    • Structural basis for MyoD and β-catenin binding undefined
  6. 2009 High

    Genetically separated the nuclear coactivator activity from receptor inhibition using a forced-nuclear SMAD7 chimera.

    Evidence NLS-fusion construct, reporter and myogenic conversion assays, Co-IP showing MyoD coactivation without Smad3 suppression

    PMID:19995910

    Open questions at the time
    • Endogenous balance between nuclear and cytoplasmic pools not quantified
    • Mechanism of nuclear import in physiological settings unaddressed
  7. 2017 High

    Identified deubiquitinases that stabilize SMAD7 and linked deubiquitination to its receptor-degrading function.

    Evidence Linkage-specific ubiquitination assays, K33/K220 mutagenesis, Co-IP, and reciprocal knockdown for OTUD1 and USP26

    PMID:28381482 PMID:29235476

    Open questions at the time
    • Tissue contexts where each DUB dominates not delineated
    • Cross-talk between OTUD1/USP26 and HERC3-driven degradation unresolved
  8. 2017 High

    Established SMAD7 as a direct amplifier of LIF/STAT3 signaling through gp130 binding, independent of TGF-β receptors.

    Evidence Co-IP, domain binding, disruption of SHP2/SOCS3-gp130 complexes, and ESC self-renewal/reprogramming assays

    PMID:28874583

    Open questions at the time
    • Whether gp130 binding occurs in non-stem-cell contexts not tested here
    • Quantitative competition with SHP2/SOCS3 not measured
  9. 2020 High

    Provided a structural rationale for SMAD7's broad inhibitory activity via a unique MH2-domain surface.

    Evidence 1.9 Å X-ray crystal structure of the mouse Smad7 MH2 domain with structural comparison to Smad6/R-Smads

    PMID:33166654

    Open questions at the time
    • No co-structure with a type I receptor
    • Functional residues not validated by mutagenesis in this study
  10. 2021 High

    Showed a post-translational modification (PRMT5 Arg-57 methylation) tunes SMAD7's gp130/STAT3 amplifier function.

    Evidence In vitro methylation, R57 mutagenesis, Co-IP, PRMT5 depletion, and STAT3 activation readouts

    PMID:34026434

    Open questions at the time
    • Interplay between Arg-57 methylation and lysine acetylation/ubiquitination unknown
    • Whether methylation affects receptor-inhibitory functions untested
  11. 2020 High

    Linked SMAD7 to fibrogenic ErbB signaling restraint, broadening its anti-fibrotic mechanism beyond Smad inhibition.

    Evidence Co-IP, myofibroblast-specific conditional KO with infarct model, unbiased transcriptomics and proteomics showing ErbB2 binding

    PMID:34905511

    Open questions at the time
    • Direct structural interface with ErbB2 not defined
    • Relative weight of ErbB versus Smad effects in fibrosis not partitioned
  12. 2024 High

    Demonstrated that SMAD7 in myofibroblasts restrains fibrosis and inflammation through paracrine matricellular signaling in vivo.

    Evidence Myofibroblast-specific conditional KO (TAC model), secretomics, MMP2 activity and macrophage co-culture assays

    PMID:38899461

    Open questions at the time
    • Direct molecular control of secreted factors by SMAD7 not mapped
    • Whether paracrine effect depends on receptor inhibition or other functions unclear
  13. 2018 High

    Established a systemic physiological role: hepatic SMAD7 negatively regulates iron homeostasis by restraining BMP-Smad-driven hepcidin.

    Evidence Hepatocyte-specific KO with iron/hepcidin measurements, phospho-Smad1/5/8 analysis, RNA-seq; prior hepcidin promoter mutagenesis

    PMID:20040761 PMID:29575577

    Open questions at the time
    • The promoter motif mediating SMAD7-dependent hepcidin suppression not mechanistically connected to receptor inhibition
    • Tissue-autonomous versus systemic contributions partly unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SMAD7's competing post-translational modifications, multiple non-canonical partners, and tissue-specific transcriptional control are integrated to select among its receptor-inhibitory versus coactivator functions in a given cell remains unresolved.
  • No unified model linking modification state to functional output
  • No co-structure of SMAD7 bound to a type I receptor or to its non-canonical partners
  • Quantitative partitioning between nuclear and receptor-proximal pools in vivo lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3 GO:0140110 transcription regulator activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3
Partners
ERBB2GADD34GP130MYODOTUD1P300PP1CSMURF2

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Smad7 mRNA is rapidly and directly induced by TGF-β1, activin, and BMP-7, and antisense Smad7 increases TGF-β1 effects, establishing Smad7 as a negative feedback regulator of TGF-β/BMP signaling. Antisense RNA expression, mRNA induction assays Biochemical and biophysical research communications Medium 9712726
1998 Xenopus Smad7 inhibits both activin and BMP pathways by associating with type I receptors and acts as a neural inducer in embryos by blocking BMP-4 signaling, with dosage-dependent effects on mesoderm specification. Animal cap explant assays, in vivo microinjection, embryological gain-of-function Developmental biology Medium 9640328
1998 Xenopus Smad7 blocks ALK-4-mediated mesoderm induction in a graded fashion and directly activates neural markers in ectodermal explants independent of mesoderm. Xenopus animal cap explants, ectopic Smad7 expression, marker gene analysis Developmental biology Medium 9705232
2002 Smad7 interacts with the transcriptional coactivator p300, leading to acetylation of Smad7 on two N-terminal lysine residues; acetylation stabilizes Smad7 by preventing ubiquitination of the same lysines by the E3 ligase Smurf1, revealing a competition between acetylation and ubiquitination for Smad7 stability. Co-immunoprecipitation, in vitro acetylation assay, mutagenesis of lysine residues, ubiquitination assay Molecular cell High 12408818
2002 YAP65 (YAP1) physically interacts with Smad7 via the Smad7 PY motif and additional domains, augments Smad7 association with activated TβRI, and potentiates Smad7 inhibitory activity against TGF-β/Smad3/4-dependent gene transactivation. Yeast two-hybrid screen, co-immunoprecipitation of co-expressed tagged proteins in COS-7 cells, deletion mutagenesis, reporter assays Oncogene Medium 12118366
2004 Smad7 acts as an adaptor protein recruiting GADD34 (a regulatory subunit of PP1 holoenzyme) and thereby the catalytic subunit PP1c to TβRI, resulting in dephosphorylation of TβRI and providing a negative feedback mechanism; SARA enhances recruitment by controlling PP1c subcellular localization. Co-immunoprecipitation, RNA interference knockdown, in vitro phosphatase assay with PP1 inhibitor The Journal of cell biology High 14718519
2004 Ski represses basal Smad7 promoter activity in a SBE-dependent manner; Ski and Smad4 bind together to the endogenous Smad7 promoter; RNAi knockdown of Ski elevates endogenous Smad7 mRNA levels. Luciferase reporter assay, chromatin immunoprecipitation (ChIP), SBE mutagenesis, RNAi knockdown The Journal of biological chemistry High 15128733
2006 Smad7 independently of its anti-Smad signaling role binds β-catenin and recruits E3 ligase Smurf2 to the Smad7/β-catenin complex, promoting β-catenin degradation and suppression of Wnt/β-catenin signaling, thereby shifting skin differentiation from hair follicles toward sebaceous glands. Co-immunoprecipitation, transgenic mouse model (Smad7 overexpression and Smurf2 co-expression), Smad7 siRNA knockdown, Wnt reporter assays Developmental cell High 16950122
2006 Smad7 promotes skeletal muscle differentiation by directly interacting with MyoD and enhancing MyoD transcriptional activity; MyoD binds and transactivates the Smad7 proximal promoter, creating a positive feedback loop; siRNA knockdown of endogenous Smad7 inhibits C2C12 differentiation. Co-immunoprecipitation, siRNA knockdown, MyoD promoter transactivation assay, myogenesis phenotypic assay Molecular and cellular biology High 16880533
2006 Smad7 and protein phosphatase 1α (PP1α) are specifically induced by TGF-β/ALK1 in endothelial cells; Smad7 and PP1α interact, PP1α interacts with ALK1, and this interaction is potentiated by Smad7; ectopic Smad7 or PP1α inhibits TGF-β/ALK1-induced Smad1/5 phosphorylation, while siRNA knockdown of either enhances it. Co-immunoprecipitation, siRNA knockdown, ectopic expression, kinase/phosphatase assays, PP1 inhibitor treatment BMC cell biology Medium 16571110
2009 Smad7 has a nuclear coactivator function independent of TGF-β receptor binding: a nuclear-localized Smad7 (NLS chimera) does not suppress Smad3 activation but retains the ability to enhance myogenic gene activation by interacting with MyoD and antagonizing repressive MEK effects on MyoD. Nuclear localization signal (NLS) fusion construct, reporter assays, co-immunoprecipitation, myogenic conversion assay Molecular and cellular biology High 19995910
2009 SMAD7 is a potent suppressor of hepcidin expression; SMAD7 overexpression abolishes hepcidin activation by BMPs and TGF-β; a distinct SMAD regulatory motif (GTCAAGAC) in the hepcidin promoter mediates SMAD7-dependent hepcidin suppression, distinct from the hemojuvelin/BMP-responsive elements. High-throughput siRNA screen, overexpression in primary hepatocytes, promoter mutational analysis Blood Medium 20040761
2017 OTUD1 directly deubiquitinates SMAD7 by cleaving Lysine 33-linked poly-ubiquitin chains on SMAD7 Lysine 220, preventing SMAD7 degradation; deubiquitination exposes the SMAD7 PY motif, enabling SMURF2 binding and subsequent TβRI turnover at the cell surface. Co-immunoprecipitation, deubiquitination assay, mutagenesis of ubiquitin linkage sites (K33, K220), loss-of-function screen in mice Nature communications High 29235476
2017 USP26 deubiquitinates and stabilizes SMAD7; TGF-β induces USP26 expression; knockdown of USP26 degrades SMAD7, stabilizes TGF-β receptor, and enhances p-SMAD2 levels. USP26 knockdown, overexpression, co-immunoprecipitation, p-SMAD2 level measurement EMBO reports Medium 28381482
2017 Smad7 activates STAT3 signaling to maintain mouse ESC pluripotency independently of TGF-β receptors but dependently on LIF co-receptor gp130; Smad7 directly binds the intracellular domain of gp130 and disrupts SHP2-gp130 or SOCS3-gp130 complexes, amplifying STAT3 activation. Co-immunoprecipitation, domain binding assays, ESC self-renewal and iPSC reprogramming assays, genetic rescue Proceedings of the National Academy of Sciences of the United States of America High 28874583
2020 Crystal structure of the MH2 domain of mouse Smad7 at 1.9 Å resolution reveals a unique three-finger-like structure (residues 331-361, 379-387, and the L3 loop) stabilized by a hydrogen-bond network; this surface is distinct from the basic groove shared with Smad6 and R-Smads, providing a structural basis for Smad7's broader inhibitory activity against all seven TGF-β family type I receptors. X-ray crystallography (1.9 Å resolution), structural comparison Journal of structural biology High 33166654
2020 Smad7 interacts with ErbB2 in a TGF-β-independent manner and restrains ErbB1/ErbB2 activation, suppressing fibroblast expression of fibrogenic proteases, integrins, and CD44; Smad7 also deactivates Smad2/3 and non-Smad TGF-β pathways without affecting TGF-β receptor activity in cardiac myofibroblasts. Co-immunoprecipitation (Smad7-ErbB2), myofibroblast-specific conditional Smad7 knockout, unbiased transcriptomics and proteomics, mouse model of non-reperfused infarction The Journal of clinical investigation High 34905511
2021 PRMT5 methylates Smad7 on Arg-57 (symmetric dimethylation), enhancing Smad7 binding to the IL-6 co-receptor gp130, thereby ensuring robust STAT3 activation; Smad7 depletion blocks PRMT5-mediated STAT3 activation. Co-immunoprecipitation, in vitro methylation assay, arginine mutagenesis (Arg-57), PRMT5 depletion/inhibition, STAT3 activation readout Advanced science High 34026434
2020 Mesenchymal MACF1 directly interacts with SMAD7 and facilitates SMAD7 nuclear translocation to initiate downstream osteogenic pathways; conditional Macf1 knockout in mesenchymal stem cells decreases osteogenic differentiation. Co-immunoprecipitation (MACF1-SMAD7), conditional gene knockout, nuclear translocation assay, osteogenic differentiation assay Cells Medium 32143362
2022 TAZ interacts with Smad7 and β-catenin in myoblasts and represses myogenic differentiation; TAZ becomes hyperphosphorylated at Ser89 during differentiation, leading to cytoplasmic sequestration; TAZ exhibits liquid-liquid phase separation properties in the nucleus. Co-immunoprecipitation (TAZ-Smad7, TAZ-β-catenin), ectopic TAZ expression, TAZ depletion, live-cell imaging (LLPS), Ser89 phosphorylation analysis Journal of cell science Medium 34859820
2017 HDAC5 interacts with MEF2A to suppress MEF2A binding to the Smad7 promoter, repressing Smad7 promoter activity and thereby maintaining TGF-β1-induced Smad2/3 phosphorylation; Smad7 knockdown rescues the reduction in Smad2/3 phosphorylation caused by HDAC5 deficiency. Luciferase reporter assay, ChIP-qPCR, siRNA knockdown of HDAC5 and Smad7, in vivo hypertrophic scar model International journal of biological sciences Medium 36263180
2019 HERC3 promotes ubiquitination-mediated degradation of SMAD7 in an autolysosome-dependent manner; HERC3 overexpression increases p-SMAD2/3 and activates the TGF-β pathway, inducing EMT in glioblastoma cells. Isobaric proteomics (iTRAQ), Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, intracranial xenograft Clinical cancer research Medium 30862693
2019 TIEG1 directly binds a GC-box/Sp1 site (nucleotides -1392 to -1382) in the Smad7 promoter to repress Smad7 transcription; TIEG1 knockdown increases Smad7 promoter activity and protein expression, while overexpression decreases them; TIEG1-mediated Smad7 suppression promotes TGF-β1-driven Smad2 phosphorylation. Luciferase reporter assay, chromatin immunoprecipitation (ChIP), siRNA knockdown and overexpression The Journal of investigative dermatology Medium 28108300
2024 In cardiac fibroblasts, Smad7 loss accentuates secretion of MMP2, and Smad7 overexpression reduces MMP2 levels; Smad7 suppresses macrophage activation through paracrine effects mediated by fibroblast-derived matricellular proteins (CD5L, SPARC, CTGF, ECM1, TGFBI); myofibroblast-specific Smad7 KO increases mortality, fibrosis, and dysfunction after pressure overload. Myofibroblast-specific conditional Smad7 KO (transverse aortic constriction model), secretomic analysis, collagen lattice contraction assay, MMP2 activity assay, macrophage co-culture Circulation research High 38899461
2023 Overexpressed Smad7 physically binds to IκBα and inhibits its ubiquitination, thereby preventing NF-κB signaling activation in microglia. Co-immunoprecipitation (Smad7-IκBα), ubiquitination assay, Cx3cr1-Smad7 AAV overexpression model, neuroinflammation phenotypic readout Molecular therapy Medium 36739479
2014 SMAD7 promotes beta-cell proliferation by increasing CyclinD1 and CyclinD2 and inducing nuclear exclusion of p27; M2 macrophage-derived TGF-β1 and EGF cooperate to induce SMAD7 upregulation and inhibit SMAD2 nuclear translocation in beta cells. Beta-cell-specific Smad7 mutant mice (PDL model), SMAD7 forced expression in beta cells in vivo, blockade of macrophage infiltration, CyclinD1/D2 and p27 protein analysis Proceedings of the National Academy of Sciences of the United States of America Medium 24639504
2009 Smad7 overexpression blocks Smad2 phosphorylation induced by bleomycin in mouse lungs and prevents lung fibrosis (suppression of type I procollagen mRNA and hydroxyproline content), while Smad6 overexpression does not. Adenoviral gene transfer of Smad7 (vs Smad6) in mouse bleomycin lung fibrosis model, Smad2 phosphorylation analysis, hydroxyproline content measurement The Journal of clinical investigation Medium 10393693
2008 Smad7 mutant mice with deletion of the MH2 domain develop cardiovascular defects (ventricular septal defect, non-compaction, outflow tract malformation) with elevated Smad2/3 phosphorylation in atrioventricular cushion and increased apoptosis in that region. Targeted deletion of MH2 domain in mice, cardiac histology, Smad2/3 phosphorylation analysis, apoptosis assay The Journal of biological chemistry Medium 18952608
2018 Hepatocyte-specific Smad7 knockout mice show decreased serum and tissue iron, increased hepcidin and phospho-Smad1/5/8, and mild iron-deficiency anemia due to reduced intestinal ferroportin, demonstrating Smad7 as a key negative regulator of iron homeostasis via BMP-Smad signaling. Hepatocyte-specific Smad7 knockout mice, serum iron/hepcidin measurements, phospho-Smad1/5/8 analysis, RNA-seq, in vitro overexpression of compensatory genes Journal of cellular and molecular medicine High 29575577

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Regulation of TGF-beta signaling by Smad7. Acta biochimica et biophysica Sinica 368 19352540
1999 Transient gene transfer and expression of Smad7 prevents bleomycin-induced lung fibrosis in mice. The Journal of clinical investigation 345 10393693
2002 Control of Smad7 stability by competition between acetylation and ubiquitination. Molecular cell 306 12408818
1998 Induction of inhibitory Smad6 and Smad7 mRNA by TGF-beta family members. Biochemical and biophysical research communications 301 9712726
2014 M2 macrophages promote beta-cell proliferation by up-regulation of SMAD7. Proceedings of the National Academy of Sciences of the United States of America 269 24639504
2008 Hepatocyte-specific Smad7 expression attenuates TGF-beta-mediated fibrogenesis and protects against liver damage. Gastroenterology 242 18602923
2004 GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor. The Journal of cell biology 209 14718519
2002 Deficient Smad7 expression: a putative molecular defect in scleroderma. Proceedings of the National Academy of Sciences of the United States of America 185 11904440
2011 Smad7: not only a regulator, but also a cross-talk mediator of TGF-β signalling. The Biochemical journal 182 21269274
2002 Yes-associated protein (YAP65) interacts with Smad7 and potentiates its inhibitory activity against TGF-beta/Smad signaling. Oncogene 175 12118366
2006 Smad7-induced beta-catenin degradation alters epidermal appendage development. Developmental cell 133 16950122
2004 Smad7 in TGF-beta-mediated negative regulation of gut inflammation. Trends in immunology 122 15364052
2008 Smad7 as a therapeutic agent for chronic kidney diseases. Frontiers in bioscience : a journal and virtual library 108 18508563
2017 Breast cancer metastasis suppressor OTUD1 deubiquitinates SMAD7. Nature communications 107 29235476
2022 Smad7 effects on TGF-β and ErbB2 restrain myofibroblast activation and protect from postinfarction heart failure. The Journal of clinical investigation 104 34905511
2008 TGF-beta1 and Smad7 in the regulation of IBD. Mucosal immunology 104 19079231
2007 Smad7 gene therapy ameliorates an autoimmune crescentic glomerulonephritis in mice. Journal of the American Society of Nephrology : JASN 101 17475816
2019 Bardoxolone ameliorates TGF-β1-associated renal fibrosis through Nrf2/Smad7 elevation. Free radical biology & medicine 95 31059771
1998 Xenopus Smad7 inhibits both the activin and BMP pathways and acts as a neural inducer. Developmental biology 93 9640328
2009 SMAD7 controls iron metabolism as a potent inhibitor of hepcidin expression. Blood 92 20040761
2008 Smad7 is required for the development and function of the heart. The Journal of biological chemistry 92 18952608
2019 HERC3-Mediated SMAD7 Ubiquitination Degradation Promotes Autophagy-Induced EMT and Chemoresistance in Glioblastoma. Clinical cancer research : an official journal of the American Association for Cancer Research 89 30862693
2013 The dual role of Smad7 in the control of cancer growth and metastasis. International journal of molecular sciences 82 24317436
2016 Smad7 gene delivery prevents muscle wasting associated with cancer cachexia in mice. Science translational medicine 79 27440729
2013 Preventive and therapeutic effects of Smad7 on radiation-induced oral mucositis. Nature medicine 74 23475202
2017 Targeted AAV5-Smad7 gene therapy inhibits corneal scarring in vivo. PloS one 72 28339457
2018 Transforming Growth Factor-β1/Smad7 in Intestinal Immunity, Inflammation, and Cancer. Frontiers in immunology 71 29973939
2020 Current perspectives on inhibitory SMAD7 in health and disease. Critical reviews in biochemistry and molecular biology 70 33081543
2014 A functional role for Smad7 in sustaining colon cancer cell growth and survival. Cell death & disease 69 24556688
2020 Role of TGF-Beta and Smad7 in Gut Inflammation, Fibrosis and Cancer. Biomolecules 65 33375423
2006 Smad7 promotes and enhances skeletal muscle differentiation. Molecular and cellular biology 65 16880533
2007 Smad7 gene transfer inhibits peritoneal fibrosis. Kidney international 64 17851465
2018 Combination of Asiatic Acid and Naringenin Modulates NK Cell Anti-cancer Immunity by Rebalancing Smad3/Smad7 Signaling. Molecular therapy : the journal of the American Society of Gene Therapy 62 30017880
2017 USP26 regulates TGF-β signaling by deubiquitinating and stabilizing SMAD7. EMBO reports 61 28381482
2022 Aberrant Nuclear Export of circNCOR1 Underlies SMAD7-Mediated Lymph Node Metastasis of Bladder Cancer. Cancer research 59 35395674
2020 Activation of Canonical BMP4-SMAD7 Signaling Suppresses Breast Cancer Metastasis. Cancer research 57 31941699
2011 Smad7 expression in T cells prevents colitis-associated cancer. Cancer research 56 22028324
2006 Decreased expression of inhibitory SMAD6 and SMAD7 in keloid scarring. Journal of plastic, reconstructive & aesthetic surgery : JPRAS 53 16676428
2019 SETDB1 regulates SMAD7 expression for breast cancer metastasis. BMB reports 52 30545440
2017 Smad7 enables STAT3 activation and promotes pluripotency independent of TGF-β signaling. Proceedings of the National Academy of Sciences of the United States of America 51 28874583
2022 HDAC5-mediated Smad7 silencing through MEF2A is critical for fibroblast activation and hypertrophic scar formation. International journal of biological sciences 50 36263180
2005 Smad7 gene transfer attenuates adventitial cell migration and vascular remodeling after balloon injury. Arteriosclerosis, thrombosis, and vascular biology 48 15860740
2023 Astrocyte-derived exosomal lncRNA 4933431K23Rik modulates microglial phenotype and improves post-traumatic recovery via SMAD7 regulation. Molecular therapy : the journal of the American Society of Gene Therapy 47 36739479
2021 miR-21-5p/SMAD7 axis promotes the progress of lung cancer. Thoracic cancer 47 34254453
2019 Smad7 Controls Immunoregulatory PDL2/1-PD1 Signaling in Intestinal Inflammation and Autoimmunity. Cell reports 47 31553906
2006 Smad7 and protein phosphatase 1alpha are critical determinants in the duration of TGF-beta/ALK1 signaling in endothelial cells. BMC cell biology 47 16571110
2014 SMAD7: a timer of tumor progression targeting TGF-β signaling. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 46 24935472
2011 Inhibitory Smad7: emerging roles in health and disease. Current molecular pharmacology 46 21222648
2003 Expression of Smad4 and Smad7 in human thyroid follicular carcinoma cell lines. Journal of endocrinological investigation 46 12952364
2021 MiR-21-3p Promotes Hepatocellular Carcinoma Progression via SMAD7/YAP1 Regulation. Frontiers in oncology 45 33763375
2017 TIEG1 Represses Smad7-Mediated Activation of TGF-β1/Smad Signaling in Keloid Pathogenesis. The Journal of investigative dermatology 44 28108300
1998 Smad7 inhibits mesoderm formation and promotes neural cell fate in Xenopus embryos. Developmental biology 44 9705232
2009 Nuclear function of Smad7 promotes myogenesis. Molecular and cellular biology 42 19995910
2018 Linc-smad7 promotes myoblast differentiation and muscle regeneration via sponging miR-125b. Epigenetics 41 29912619
2023 Smad7 in the hippocampus contributes to memory impairment in aged mice after anesthesia and surgery. Journal of neuroinflammation 40 37507781
2015 The role of Smad7 in oral mucositis. Protein & cell 39 25566830
2012 Smad7 inhibits differentiation and mineralization of mouse osteoblastic cells. Endocrine journal 39 22673292
2017 TGF-β inhibitor Smad7 regulates dendritic cell-induced autoimmunity. Proceedings of the National Academy of Sciences of the United States of America 38 28167776
2015 Genetic disruption of Smad7 impairs skeletal muscle growth and regeneration. The Journal of physiology 37 25854148
2004 Repression of endogenous Smad7 by Ski. The Journal of biological chemistry 37 15128733
2024 SMAD7 expression in CAR-T cells improves persistence and safety for solid tumors. Cellular & molecular immunology 36 38177245
2016 microRNA-497 Modulates Breast Cancer Cell Proliferation, Invasion, and Survival by Targeting SMAD7. DNA and cell biology 36 27303812
2018 Single Nucleotide Polymorphism in SMAD7 and CHI3L1 and Colorectal Cancer Risk. Mediators of inflammation 35 30498395
2021 Circular RNA circPSD3 alleviates hepatic fibrogenesis by regulating the miR-92b-3p/Smad7 axis. Molecular therapy. Nucleic acids 34 33614234
2021 Expression and function of Smad7 in autoimmune and inflammatory diseases. Journal of molecular medicine (Berlin, Germany) 33 34059951
2017 MicroRNA-21 promotes wound healing via the Smad7-Smad2/3-Elastin pathway. Experimental cell research 32 29154818
2016 MiR-181a-5p regulates 3T3-L1 cell adipogenesis by targeting Smad7 and Tcf7l2. Acta biochimica et biophysica Sinica 32 27742678
2010 Trigenic neural crest-restricted Smad7 over-expression results in congenital craniofacial and cardiovascular defects. Developmental biology 32 20457144
2024 Fibroblast Smad7 Induction Protects the Remodeling Pressure-Overloaded Heart. Circulation research 31 38899461
2016 Mongersen, an oral Smad7 antisense oligonucleotide, in patients with active Crohn's disease. Therapeutic advances in gastroenterology 31 27366221
2020 Mesenchymal stem cell-based Smad7 gene therapy for experimental liver cirrhosis. Stem cell research & therapy 29 32928296
2019 Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3. Life science alliance 29 31085559
2020 Alcohol promotes renal fibrosis by activating Nox2/4-mediated DNA methylation of Smad7. Clinical science (London, England : 1979) 28 31898747
2023 PHF14 enhances DNA methylation of SMAD7 gene to promote TGF-β-driven lung adenocarcinoma metastasis. Cell discovery 27 37072414
2016 Effect of transforming growth factor-β3 on the expression of Smad3 and Smad7 in tenocytes. Molecular medicine reports 27 26935007
2021 Exosomal MicroRNA-21 Promotes Keloid Fibroblast Proliferation and Collagen Production by Inhibiting Smad7. Journal of burn care & research : official publication of the American Burn Association 26 34146092
2021 PRMT5 Enables Robust STAT3 Activation via Arginine Symmetric Dimethylation of SMAD7. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 25 34026434
2020 Mesenchymal MACF1 Facilitates SMAD7 Nuclear Translocation to Drive Bone Formation. Cells 25 32143362
2006 Yes-associated protein (YAP65) in relation to Smad7 expression in human pancreatic ductal adenocarcinoma. International journal of molecular medicine 25 16596258
2022 Ginsenoside Rg1 Epigenetically Modulates Smad7 Expression in Liver Fibrosis via MicroRNA-152. Journal of ginseng research 24 37397418
2019 Smad7 and Colorectal Carcinogenesis: A Double-Edged Sword. Cancers 24 31052449
2017 Smad7 positively regulates keratinocyte proliferation in psoriasis. The British journal of dermatology 24 28580633
2016 miR-21 promotes collagen production in keloid via Smad7. Burns : journal of the International Society for Burn Injuries 24 27717618
2013 Sma- and Mad-related protein 7 (Smad7) is required for embryonic eye development in the mouse. The Journal of biological chemistry 24 23426374
2017 Smad7 knockdown activates protein kinase RNA-associated eIF2α pathway leading to colon cancer cell death. Cell death & disease 23 28300830
2023 FOXO3 regulates Smad3 and Smad7 through SPON1 circular RNA to inhibit idiopathic pulmonary fibrosis. International journal of biological sciences 22 37416778
2022 Nitroxoline suppresses metastasis in bladder cancer via EGR1/circNDRG1/miR-520h/smad7/EMT signaling pathway. International journal of biological sciences 22 35982887
2019 MiR-216a accelerates proliferation and fibrogenesis via targeting PTEN and SMAD7 in human cardiac fibroblasts. Cardiovascular diagnosis and therapy 22 32038943
2015 Smad7 protects against chronic aristolochic acid nephropathy in mice. Oncotarget 22 25883225
2012 Role of Smad7 in inflammatory bowel diseases. World journal of gastroenterology 22 23155305
2009 Non-viral Smad7 gene delivery and attenuation of postoperative peritoneal adhesion in an experimental model. The British journal of surgery 21 19847872
2023 Hydronidone ameliorates liver fibrosis by inhibiting activation of hepatic stellate cells via Smad7-mediated degradation of TGFβRI. Liver international : official journal of the International Association for the Study of the Liver 20 37641479
2020 Structural basis for inhibitory effects of Smad7 on TGF-β family signaling. Journal of structural biology 20 33166654
2022 TAZ exhibits phase separation properties and interacts with Smad7 and β-catenin to repress skeletal myogenesis. Journal of cell science 19 34859820
2021 Involvement of Smad7 in Inflammatory Diseases of the Gut and Colon Cancer. International journal of molecular sciences 19 33920230
2018 Smad7 deficiency decreases iron and haemoglobin through hepcidin up-regulation by multilayer compensatory mechanisms. Journal of cellular and molecular medicine 19 29575577
2018 Immunohistochemical Expression of TGF-Β1, SMAD4, SMAD7, TGFβRII and CD68-Positive TAM Densities in Papillary Thyroid Cancer. Open access Macedonian journal of medical sciences 19 29610597
2000 Expression of the inhibitory Smad7 in early mouse development and upregulation during embryonic vasculogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 19 10906784
2017 CREB1 and Smad3 mediate TGF‑β3‑induced Smad7 expression in rat hepatic stellate cells. Molecular medicine reports 18 28983617
2022 CDCA7 promotes TGF-β-induced epithelial-mesenchymal transition via transcriptionally regulating Smad4/Smad7 in ESCC. Cancer science 17 36056599

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