Poster

Modeling Cellular Signaling and Mesangial Fibrosis during Diabetic Kidney

eSMB2020 eSMB2020 Follow 2:30 - 3:30pm EDT, Monday - Wednesday
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Haryana Thomas

Oklahoma State University
"Modeling Cellular Signaling and Mesangial Fibrosis during Diabetic Kidney"
In the U.S. alone over 250,000 people use dialysis or have received a kidney transplant due to diabetic kidney failure. Although we have come a long way in the treatment of diabetes, kidney failure due to diabetic kidney damage is still prevalent, and the need for increasing our understanding of kidney damage to enable the development of better treatment methods is ever present. Thus the goal of this research is to develop computational models to better understand the kidney damage that occurs due to diabetic kidney disease. In the kidney glomerulus lies a network of capillaries that are surrounded by interstitial tissue called the mesangium. In health, the mesangium acts as a support for the capillaries; however, during diabetic kidney disease, the mesangium expands due to excess accumulation of collagen and causes damage to the cellular environment around it. This mesangial expansion is not only a hallmark of kidneys damaged by diabetes but also many other chronic kidney diseases that lead to kidney failure. As such there has been a lot of research effort in trying to figure out the cause of the mesangial expansion. Researchers have found high glucose-induced dysfunction in the mesangial cell, a cell native to the mesangium, to be one of the main reasons for mesangial expansion. The mesangial cell dysfunction is mediated by the overstimulation of key signaling and cellular communication molecules such as TGF-B, and Ang II which play a key role in perturbing the function of downstream collagen metabolism molecules such as MMP, and TIMP leading to the accumulation of excess collagen. The complexity of the interactions necessitates the development of computational models to understand the whole, yet there are few computational models of mesangial expansion and even fewer that study the effect of the mesangial expansion on cellular communication and signaling in the glomerulus. In this work, we present a computational model of mesangial expansion to study its effect on cellular signaling. Previously, researchers have developed computational models of mesangial expansion to understand its impact on the accumulation of certain macromolecules whose accumulation has been shown to lead to glomerular damage. Our computational model builds on such a model to elucidate the impact of mesangial cell mediated mesangial expansion on cellular signaling through multiscale modeling of ECM remodeling and macromolecular transport. We are extending the previous model by incorporating a cellular environment using the Cellular Potts model, modeling mesangial expansion using fundamental biological principles of collagen fiber growth and accumulation, solving macromolecular transport equations using a solver and linking them all using python and CompuCell3D, a multiscale tissue simulation software. The model captures mesangial expansion and provides insight into cellular communication.
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Virtual conference of the Society for Mathematical Biology, 2020.