Endothelial to mesenchymal transition (EndoMT) and an increase expression of the genes actin alpha 2 smooth muscle aorta (ACTA2
), CTNNB1 ([beta]-cateninin), Snail Family Transcriptional Repressor 1 (SNAI1) and hyaturonan synthase (HAS2) has been determined in canine MMVD valves.
This resulted in an increased expression of PLOD2, Alpha Smooth Muscle Actin (ACTA2
), and collagen type 1 (COL1A1), which are all associated with fibrosis (Remst et al., 2014).
Eighty-eight transcription regulators were found in the adipose tissue between 18 vs 24, KLF5, one of activated transcription regulators, which is relevant to cancer, cellular development, cellular growth and proliferation, and this regulator is unregulated FAM110A, MYC, DUSP1, ACTA2
, NOTCH1 and PREB, down regulated RUNX1 (Fig.
These genes encoded proteins primarily involved in integrin signalling pathways (ACTA2
, PIK3C2G, COL4A6, CAV1, LAMA1, FN1, and ITGA8), regulation of hormone levels (NR5A1, TIPARP, ACE, CRYM, CGA, ALDH1A1, TBX3, POMC, GHRH, and ALDH6), camera-type eye development (TGFBR2, BMP4, FABP7, STRA6, SIX6, and WNT6), blood vessel development (Figure S1, goo.gl/tC9GTZ), and regulation of cellular response to growth factor stimulus (see Figure 2).
hMSCs cultured in 3D/FN structures for 28 days expressed both endothelial cell (MCAM, VCAM) and smooth muscle cell markers (ACTA2
, TAGLN) indicating that exogenous, full-length fibronectin protein presented in 3D can trigger differentiation of hMSCs into these two cell types (Figures 4(c) and 4(d)).
Remarkably, PFD + M-DDO patients showed a 110-fold increase in ACTA2
gene expression (p = 0.019), which codifies for alpha-smooth muscle actin ([alpha]-SMA), a contractile protein.
The top 15 hub genes, possessing high degree of connectivity in DCM, are as follows: IL6, MYC, ACTA2
, SERPINE1, ASPN, SPP1, KIT, TFRC, FMOD, PDE5A, MYH6, FPR1, C3, CDKN1A, and SOCS3.
Meanwhile, the mRNA expression levels of Acta2
, MMP13, Coll1a1, and TIMP1 were examined, which are all classical profibrogenic markers during liver fibrosis process [16, 17].
In addition, certain gene mutations (GATA5, NOTCH1, ACTA2
) are associated with BAV defect, leaflet calcification and aortic dilation.
Other studies have suggested that the ACTA2
gene, calcium signals, cadherin 6B, and integrin receptor may also participate in this pathophysiological process [96, 99-101].
Genetics testing of the following genes was performed, though no pathogenic mutations or clinically significant variants were detected: ACTA2
, CBS, COL3A1, FBN1, FBN2, MYH11, SLC2A10, SMAD3, TGFBR1 and TGFBR2.