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. 2021 Mar 24;320(6):G936–G957. doi: 10.1152/ajpgi.00053.2021

Table 3.

Junctional protein-related genes are altered with loss of epithelial Smad4 expression in vivo and with TGFβ pathway stimulation in vitro

SMAD4 KO In Vivo
 TGFβ1/BMP2 Treatment In Vitro
Gene Symbol (Protein Name) Fold Change Log2 Fold Change P Value FDR Fold Change Log2 Fold Change P Value FDR
Tight Junction Tjp1 (ZO-1) 1.64 0.71 <0.001 <0.001 1.71 0.78 <0.001 <0.001
Tjp2 (ZO-2) 1.30 0.38 0.005 0.016 1.85 0.89 <0.001 <0.001
Ocln (Occludin) 0.85 −0.24 0.109 0.198 1.35 0.43 0.023 0.051
Cldn2 (Claudin 2) 1.22 0.28 0.045 0.098 0.06 −4.14 <0.001 <0.001
Cldn3 (Claudin 3) 0.56 −0.85 <0.001 <0.001 1.29 0.37 0.040 0.081
Cldn4 (Claudin 4) 0.64 −0.64 0.002 0.007 5.79 2.53 <0.001 <0.001
Cldn7 (Claudin 7) 0.82 −0.29 0.041 0.092 1.49 0.58 0.002 0.004
Cldn8 (Claudin 8) 2.13 1.09 <0.001 <0.001 0.06 −4.10 <0.001 <0.001
Cldn10 (Claudin 10) 10.45 3.39 <0.001 <0.001
Cldn12 (Claudin 12) 1.11 0.15 0.323 0.454 0.81 −0.31 0.112 0.188
Cldn14 (Claudin 14) 1.04 0.06 0.821 0.882 0.12 −3.02 <0.001 <0.001
Cldn15 (Claudin 15) 0.53 −0.91 <0.001 <0.001 0.06 −4.09 <0.001 <0.001
Cldn23 (Claudin 23) 1.03 0.04 0.796 0.865 3.66 1.87 <0.001 <0.001
Cldn25 (Claudin 25) 0.91 −0.13 0.316 0.447 1.45 0.54 0.013 0.033
Marveld2 (Tricellulin) 1.04 0.06 0.642 0.747 1.51 0.59 0.009 0.023
Adherens Junction Cdh1 (E-Cadherin) 1.27 0.35 0.012 0.033 2.54 1.35 <0.001 <0.001
Ctnna1 (α-1-Catenin) 1.15 0.20 0.142 0.242 2.31 1.21 <0.001 <0.001
Ctnnb1 (β-Catenin) 0.99 −0.01 0.929 0.958 2.11 1.08 <0.001 <0.001
Ctnnd1 (P120 Catenin) 1.47 0.56 <0.001 <0.001 3.20 1.68 <0.001 <0.001
Jup (Plakoglobulin) 0.93 −0.11 0.495 0.622 3.39 1.76 <0.001 <0.001
Pkp1 (Plakophilin 1) 1.03 0.04 0.771 0.845 2.70 1.43 <0.001 <0.001
Pkp2 (Plakophilin 2) 1.36 0.44 <0.001 0.002 1.65 0.72 <0.001 0.001
Pkp3 (Plakophilin 3) 0.66 −0.59 <0.001 <0.001 2.85 1.51 <0.001 <0.001
Vcl (Vinculin) 1.27 0.34 0.012 0.032 1.79 0.84 <0.001 <0.001
Actn1 (Actinin Alpha 1) 1.74 0.80 <0.001 <0.001 2.93 1.55 <0.001 <0.001
Actn4 (Actinin Alpha 4) 1.09 0.13 0.405 0.539 2.50 1.32 <0.001 <0.001
Desmosome Dsc2 (Desmocollin 2) 1.40 0.49 0.001 0.005 2.89 1.53 <0.001 <0.001
Dsg2 (Desmoglein 2) 1.51 0.59 <0.001 <0.001 2.25 1.17 <0.001 <0.001
Dsg3 (Desmoglein 3) 9.13 3.19 <0.001 <0.001
Gap Junction Gjb4 (Connexin 30.3) 14.1 3.82 <0.001 <0.001
Gjb3 (Connexin 31) 0.75 −0.42 0.003 0.010 3.20 1.68 <0.001 <0.001
Gjb5 (Connexin 31.1) 9.19 3.20 <0.001 <0.001
Gjb1 (Connexin 32) 0.80 −0.32 0.010 0.028 0.35 −1.51 <0.001 <0.001
Gja5 (Connexin 40) 29.0 4.86 <0.001 <0.001
Gja1 (Connexin 43) 2.19 1.13 0.012 0.032 0.46 −1.12 0.002 0.005
Cell Adhesion Molecules Ceacam1 (Carcinoembryonic Antigen-related Cell Adhesion Molecule 1) 1.54 0.63 <0.001 <0.001 2.33 1.22 <0.001 <0.001
Ceacam10 (Carcinoembryonic Antigen-related Cell Adhesion Molecule 10) 1.35 0.43 0.007 0.022 0.17 −2.57 <0.001 <0.001
Ceacam18 (Carcinoembryonic Antigen-related Cell Adhesion Molecule 18) 0.58 −0.79 <0.001 <0.001 2.12 1.09 0.030 0.070
Ceacam20 (Carcinoembryonic Antigen/CEA) 1.47 0.56 <0.001 0.001 2.01 1.01 <0.001 0.002
Mucins Muc1 (Mucin 1) 2.36 1.24 <0.001 <0.001 0.49 −1.02 0.066 0.123
Muc2 (Mucin 2) 0.76 −0.39 0.015 0.041 0.20 −2.34 <0.001 <0.001
Muc3 (Mucin 3) 0.98 −0.03 0.864 0.913
Muc4 (Mucin 4) 2.01 1.01 <0.001 <0.001 2.19 1.13 <0.001 <0.001
Muc13 (Mucin 13) 1.31 0.39 0.008 0.023 0.65 −0.62 0.001 0.002
Muc20 (Mucin 20) 2.07 1.05 0.006 0.019

Comparison of two RNA-sequencing (RNA-seq) datasets. Left columns titled “SMAD4 KO in vivo” represent RNA-seq data comparing gene expression in the colon epithelium of three Smad4ΔLrig1 and three control mice. Right columns titled “TGFβ1/BMP2 Treatment in vitro” represent RNA-seq data comparing gene expression in wild-type colonoids treated with TGFβ1 + BMP2 or vehicle × 24 h (three biological replicates). Rows bolded represent genes that are significantly changed (P < 0.05) in opposite directions with SMAD4 knockout in vivo and TGFβ/BMP treatment in vitro, suggesting a possible role for direct regulation by canonical TGFβ signaling. BMP, bone morphogenetic protein; FDR, false discover rate; KO, knockout; TGFβ, transforming growth factor-β.