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Table 1 Overview of mouse studies with altered expression of Smad7

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]