Fig. 5

The role of RDGN in human diseases. DACH1 is required for the elongation of the coronary artery. DACH1 stimulates coronary artery endothelial cells (CECs) proliferation and promotes the migration of CECs by up-regulating CXCL12. Moreover, the overexpressed DACH1 in capillary endothelial cells promotes arterial normalization and prolongs arterial branches. The overexpression of EYA2 directly activates mTOR, leading to cardiac hypertrophy. In the hormonal system, DACH1 is linked to islet development, and insulin secretion, proving that DACH1 is involved in the pathogenesis of type-2 diabetes. In the urinary system, knocked down the expression of DACH1 caused damage to the kidney podocytes and tubular cells, eventually leading to CKD. Moreover, DACH1 knockout mice are more likely to aggravate the progress of diabetes nephropathy. DACH1 inhibits the expression of ATF6 and reduces tissue-type plasminogen activator (tPA) in mouse liver cells, reducing the risk of thrombosis. In the nervous system, DACH1 is a specific marker for neuroepithelial and ventricular radial glial cells. DACH1 is identified as one of the driver genes for postaxial polydactyly in the locomotor system. After denervation, lower DACH2 is observed in adult muscle fibers, allowing myogenin and nAchR expression to be up-regulated. While overexpression of DACH2 in denervated muscle reduced Mgn, nAChR, and MuSK gene induction depending on HDAC inhibitor. In the respiratory system, overexpression of SIX1 increases macrophage migration inhibitory factor (MIF) levels and promotes pulmonary fibrosis. Six1 is up-regulated in the chronic asthma mouse model. Silencing of Six1 reduced the expression and secretion of the airway remodeling-related mediators MMP-2 and MMP-9 through inhibition of the NF-KB pathway