Table 2. Select canonical pathways with differentially expressed genes in c-Kit deficient vs. wild type smooth muscle cells.

Pathway	Biological function	P-value	Z-scorea	Predicted statusa	Differentially expressed genes
PTEN signalingb	Proliferation, apoptosis, de-differentiation, cell migration, inflammation	<0.001	0.258	Activation	Akt2, Casp3, Rac1, Ccnd1, Igf2r, Rac3, Ddr1, Shc1, Ikbkb, Inpp5f, Foxo1, Bmpr1a, Magi2, Magi3, Pdgfrb
Death receptor signalingb	Apoptosis	0.003	1.265	Activation	Map2k4, Gas2, Rock1, Diablo, Ikbkb, Casp3, Htra2, Tbk1, Parp1, Birc2
TNFR2 signalingb	Cell survival, inflammation	0.005	1.000	Activation	Map2k4, Ikbkb, Tnfaip3, Tbk1, Birc2
Wnt/ β-catenin signaling	Proliferation, cell survival, cell migration	0.008	0.577	Activation	Sfrp4, Akt2, Crebbp, Csnk1a1, Fzd9, Ccnd1, Rarg, Fzd8, Cdh5, Dkk3, Sox18, Ppp2r5e, Sfrp1, Wnt5b
IRF activation pathwayb	Inflammation	0.011	1.134	Activation	Map2k4, Ikbkb, Crebbp, Tbk1, Ifna14, Irf3, Atf2
ERK/MAPK signaling	Proliferation, cell migration, vasoconstriction	0.028	1.069	Activation	Crebbp, Rac1, Ppp1r14a, Mknk2, Rac3, Nfatc1, Atf2, Pla2g4e, Shc1, Pla2g6, Prkar2b, Prkag2, Rps6ka1, Ppp2r5e
TNFR1 signalingb	Cell survival, inflammation	0.044	1.000	Activation	Map2k4, Ikbkb, Casp3, Tnfaip3, Birc2
Wnt/Ca2+ pathwayb	Proliferation, cell migration	<0.001	−1.000	Inhibition	Fzd8, Plcb4, Crebbp, Nfatc2, Fzd9, Nfatc4, Wnt5b, Nfatc1, Atf2
AMPK signalingb	Cellular senescence, anti-inflammatory, differentiation, vasoconstriction	<0.001	−0.535	Inhibition	Pbrm1, Akt2, Crebbp, Ccnd1, Slc2a4, Elavl1, Atf2, Ak6, Prkar2b, Foxo1, Adra2a, Ppm1b, Sirt1, Prkag2, Ppm1a, Ppp2r5e, Ppat, Camkk2
Apoptosis signalingb	Apoptosis	<0.001	−0.302	Inhibition	Map2k4, Gas2, Rock1, Diablo, Ikbkb, Casp3, Htra2, Rps6ka1, Bcl2a1, Parp1, Birc2
Phospholipase C signaling	Vasoconstriction, stress responses	0.001	−0.378	Inhibition	Rala, Arhgef12, Pld3, Fcgr2a, Arhgef15, Crebbp, Rac1, Ppp1r14a, Nfatc4, Fcgr2b, Rhoh, Nfatc1, Atf2, Pla2g6, Shc1, Pla2g4e, Plcb4, Itpr3, Fcer1g, Nfatc2
Nitric oxide/GC signaling	Vasodilation	0.005	−0.302	Inhibition	Bdkrb2, Kng1, Pde2a, Akt2, Prkg1, Prkar2b, Itpr3, Prkag2, Pde1a, Gucy1b3, Pgf
Integrin signaling	Cell adhesion, cell migration, proliferation, apoptosis, stress responses, differentiation	0.029	−1.387	Inhibition	Map2k4, Akt2, Rala, Rac1, Rac3, Rhoh, Pdgfb, Rock1, Arhgap5, Shc1, Itga11, Itga9, Actn4, Tspan6, Nedd9
Adipogenesis pathway	Lipid synthesis and storage	<0.001	N.D.	Could not be predicted	Nr2f2, Sin3b, Fzd9, Nfatc4, Rbp1, Slc2a4, Fzd8, Cdk5, Foxo1, Bmpr1a, Lpl, Sirt1, Ctbp2, Clock, Fabp4, Rps6ka1, Stat5b
Fibroblast inflammatory pathwayb	Proliferation, cell migration, differentiation, inflammation	0.012	N.D.	Could not be predicted	Map2k4, Sfrp4, Akt2, Crebbp, Csnk1a1, Rac1, Fzd9, Nfatc4, Ccnd1, Nfatc1, Pdgfb, Pgf, Atf2, Rock1, Ikbkb, Fzd8, Plcb4, Dkk3, Nfatc2, Sfrp1, Wnt5b
Gαq signalingyb	Proliferation, cell migration, vasoconstriction	0.026	0.000	Could not be predicted	Rock1, Ikbkb, Plcb4, Akt2, Pld3, Agtr1b, Itpr3, Nfatc2, Nfatc4, Avpr1a, Rhoh, Nfatc1

Notes.

^aZ-score and predicted functional status in c-Kit deficient smooth muscle cells compared to wild type cells. The z-score measures how close the gene expression data matches the experimentally observed direction of pathway regulation in the literature. A positive z-score predicts activation, while a negative z-score indicates inhibition. N.D., could not be determined.

^bNF-κB associated signaling pathway.