MZF‐1 regulates the CTGF gene in the hematopoietic compartment

Abstract

Connective Tissue Growth Factor (CTGF), an extracellular protein with key roles in wound healing and tissue homeostasis, has recently been shown to be in abundance in thrombocytes. Paradoxically, megakaryocytes, the platelet precursors in the bone marrow, contain no detectable levels of CTGF, and the source of CTGF in platelets is yet to be determined. It has been proposed that cells in the vicinity of the megakaryocyte secrete CTGF upon cellular signaling, at which point it is then internalized by fragmenting platelets entering the vasculature.In this study, we report the discovery of a possible functional binding site for Myeloid Zinc Finger‐1 (MZF‐1), a transcription factor localized in the bone marrow, in the promoter region of the human CTGF gene, using bioinformatics. We further show that, in HeLa, HEK‐293, and select hematopoietic cells, binding of MZF‐1 to the CTGF promoter can be detected with Chromatin Immunoprecipitation (ChIP). Furthermore, we investigated the induction of CTGF by calcitriol (1,25‐ dihydroxyvitamine D3) via MZF‐1, through the PI‐3 kinase pathway in HS‐5 stromal fibroblasts, a possible candidate for the supply of CTGF to platelets entering the bloodstream. Finally, expression of CTGF is attenuated following ablation of MZF1 by miRNA. Taken together, our results argue that MZF‐1 is a key regulator of CTGF in the hematopoietic compartment, and may be a factor in the process of CTGF acquisition by thrombocytes.