Internal Medicine (MEND)

Biointerfaces Institute

Our research is focused on extracellular matrix (ECM) remodeling in obesity, diabetes, and cardiovascular diseases. In the body, metabolically active mesenchymal cells are surrounded by a fibrous meshwork of extracellular matrix proteins, e.g, collagens, elastin, and fibronectin. Embedded within these dense matrices, adipocytes and their precursor cells constantly change their shape and function in adaptation to nutritional cues by remodeling surrounding ECM. 
cell images

A membrane-type matrix metalloproteinase called MT1-MMP (MMP14) promotes adipose tissue expansion in obesity (Chun et al., Diabetes 2010). Mechanistically, MMP14-dependent collagen degradation is necessary for adipogenic histone modifications (Sato-Kusubata et al., Mol. Endocrinol. 2011). We have identified that Sca1-positive adipose stromal cells play a key role in adipose tissue ECM remodeling (Tokunaga et al., Matrix Biology 2014).  

Thrombospondin 1 (THBS1) is a matricellular ECM protein produced by visceral adipose tissues and released into circulation. THBS1 causes skeletal muscle fibrosis and insulin resistance in mice and humans (Inoue et al., Endocrinology 2013, Matsuo et al, Metabolism 2015, Lin et al, Biochem Pharmacol 2016). 

In collaboration with researchers at Biointerfaces Institute of NCRC, we have developed a prototypical on-chip adipose tissue model for better understanding of metabolic tissue crosstalk on-chip (Moraes et al., Integr Biol 2013, Akama et al, Methods Mol Biol. 2017 ). 

Our recent efforts newly identified the unexpected role played by MT1-MMP expressed by vascular smooth muscle cells (VSMC) in preventing the progression of atherosclerosis and aneurysm formation in mice (Barnes et al, J Am Heart Assoc. 2017). These in-vivo findings along with 3-D in-vitro data suggest that MT1-MMP is necessary to prevent unregulated proliferation of VSMCs in atherosclerotic lesions. 



Presentations at ENDO 2018 (Chicago), March 17-19, 2018. 

New paper is out! 

Transcription factor 21 (Tcf21) promotes proinflammatory interleukin 6 expression and extracellular matrix remodeling in visceral adipose stem cells

JBC online