HOX and MEINOX in cellular plasticity, fibrosis, and cancer

Table 4 The effects of MEINOX genes in various fibrotic diseases

MEINOX genes	Disease	Mode of function in fibrosis	Proof of concept or mechanism of action	Ref.
MEIS1	Kidney fibrosis	Pro-fibrotic	MEIS1 is strongly induced in PDGFRβ+ pericytes as they transition into myofibroblasts during acute and chronic kidney injury	[210]
	Kidney fibrosis	Anti-fibrotic	In mice, fibroblast-specific MEIS1 overexpression inhibited myofibroblast activation and attenuated renal fibrosis, whereas MEIS1 knockout in fibroblasts worsened fibrosis	[6]
PKNOX2	Kidney fibrosis	Pro-fibrotic	TGF-β1 treatment induces PKNOX2 in fibroblasts, and PKNOX2 appears to support fibrogenesis by enhancing fibroblast survival	[93]
	Cardiac fibrosis	Anti-fibrotic	In healthy human heart, PKNOX2 is associated with normal fibroblast activation, but in failing heart, its expression drops during fibroblast-to-myofibroblast transition	[11]
	Myelofibrosis	Anti-fibrotic	PKNOX2 expression is significantly downregulated in Fanconi anemia patients’ bone marrow MSCs compared to healthy controls	[43]

PDGFRβ: Platelet-derived growth factor receptor beta; TGF: Transforming growth factor; MSC: Mesenchymal stem cell.