From: Unraveling the biological functions of Smad7 with mouse models
Organ (Tissue) | Modification of Smad7 | Functions or phenotypes | Proposed mechanisms | Related disease(s) | Ref |
---|---|---|---|---|---|
Zygote | Overexpression | The embryos do not develop beyond 2-cell stage | Inhibiting TGF-β and BMP signaling | none | [14] |
Lung | Overexpression | Anti-fibrosis, anti-inflammation, tumorigenic, involved in lung branching morphogenesis and epithelial differentiation | Blocking synthesis of ECM, preventing NFκB activation and inhibiting EMT | Lung fibrosis, neonatal hyperoxia, allergic asthma and lung cancer | [15, 26, 52] |
Eyes | Over-expression | Anti-fibrosis, anti-inflammation, and improving healing from chemical burn injury | Blocking EMT and accelerating healing after injury | Retinal pigment fibrosis | [30, 58, 59] |
Skin | Overexpression | Shifting skin differentiation from hair follicles to sebaceous glands, accelerating squamous cell carcinogenesis, tumorigenic, anti-inflammation | Suppressing Wnt/β-catenin signaling, inducing EGF-like growth factors expression, blocking NFκB signaling | Scleroderma, skin cancer, inflammation | [16, 36, 49, 56] |
Liver |
Overexpression Knockout | Anti-fibrosis, anti-inflammation, inhibiting EMT and apoptosis, reducing alcoholic liver injury | Blocking ECM production, anti-oxidative stress, activating ADH1, suppressing alcoholic steatosis | Liver fibrosis, cirrhosis, alcoholic fatty liver | [32, 33, 39] |
Pancreas | Overexpression | Abolishing β-cell differentiation in embryo, inhibiting insulin secretion in adults, anti-fibrosis, inducing early tumorigenesis | Inhibiting TGF-β signaling, pro-proliferative | Pancreatic fibrosis, pancreatitis, pancreatic cancer, diabetes | [29, 50, 57] |
Kidney |
Overexpression Knockout | Anti-fibrosis, anti-inflammation, protecting against diabetic injury | Reducing ECM accumulation, blocking NFκB signaling | Nephritis, kidney fibrosis, diabetic kidney injury | [27, 28, 37, 38] |
Colon |
Overexpression Knockdown | Enhancing inflammatory reaction, increasing cancer metastasis | CD4+ T cell overactivation and resistance to regulatory T cell, reduced growth inhibition and apoptosis | IBD, colitis, colorectal cancer | [42, 51] |
CNS |
Overexpression Knockdown | Pro-inflammatory, craniofacial and cardiac defects | Promoting T cell activation, blocking Wnt, BMP and TGF-β signaling | Autoimmune encephalomyelitis, craniofacial defects | [18, 44] |
Immune cells |
Overexpression Knockout | Involved in proliferation of T cell and B cell response to antigen stimulation, pro-inflammatory, tumor suppression | Involved in immune cell maturation, proliferation and activation | Allergic asthma, autoimmune disorder, colitis, colon cancer | [19, 40, 41, 45, 55] |
Bone | Overexpression | Inhibiting chondrocyte differentiation | Down-regulating p38 MAPK pathway | Joint disease and repair | [17] |
Systemic | Knockout | Important for early heart development and B cell function | Apoptosis, inhibiting TGF-β signaling | Congenital heart defects | [19, 20] |