Extracellular transglutaminase 2 activates β‐catenin signaling in calcifying vascular smooth muscle cells

Abstract

Accumulation of transglutaminase 2 (TG2) is often associated with mineral deposits in vasculature. Here, we demonstrate that purified TG2 stimulated a 3-fold increase in matrix mineralization and up-regulation of osteoblastic markers in cultured primary vascular smooth muscle cells (VSMCs). Extracellular TG2 interacts with the low density lipoprotein relatedprotein 5 receptor and activates b-catenin signaling in VSMCs. These results suggest that TG2 may promote vascular calcification by activating the b-catenin signaling pathway.

Quercetin Attenuates Warfarin-induced Vascular Calcification in Vitro Independently from Matrix Gla Protein

“…Consistent with the above findings, warfarin-induced calcification in VSMCs does not associate with either induction of transcription factor Msx2, which regulates diabetic calcification via the BMP-Msx2 axis (46), or induction of the phosphate transporter PiT-1 and osteopontin, both of which are markers of PKA-dependent calcification (47). Our findings indicate that despite the many common features between physiologic differentiation of osteoblasts and pathologic osteoblastic transformation of VSMCs, these processes show differences that may potentially underlie the "bone-vascular paradox" in which bone loss in osteoporosis is accompanied by VC (50).…”

Angiotensin II promotes an osteoblast-like phenotype in porcine aortic valve myofibroblasts

“…Phosphorylated Dsh binds to APC, leads to inhibition of GSK-3 b, such that b-catenin will not be phosphorylated by GSK-3b. Therefore, b-catenin can accumulate in the cytoplasm and form a complex with Tcf/Lcf after its translocation into the nucleus [29], and activates downstream target gene expression, including c-myc, cyclin D1, MMP7, growth factors, and BMPs, and regulates cell growth. The transcriptional activation of these target genes after b-catenin accumulation in the nucleus is the most critical step in the canonical Wnt signaling pathway in regulating cell proliferation and differentiation.…”

Physiological, pathological, and structural implications of non-enzymatic protein–protein interactions of the multifunctional human transglutaminase 2

“…TG2 was shown to interact directly with LRP5/6 on smooth muscle cells, which in turn activate the ß-catenin pathway and regulate calcification and osteoblastic transformations in vascular smooth muscle cells [51].…”