Date of Award
Dr. Hong Zheng
Dr. Yifan Li
Dr. Curtis Kost
fibrosis, GDF15, inflammation, kidney, MIC-1, NAG-1, obesity
Biochemical Phenomena, Metabolism, and Nutrition | Nephrology
According to the World Health Organization, worldwide obesity has tripled since 1975 and is still on the rise, putting people at a higher risk of some cardiovascular diseases and kidney disease. Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine that has been studied recently for its role in multiple biological processes and diseases. The member of the transforming growth factor beta (TGF-b) family has been investigated as a therapeutic agent and biomarker for obesity and associated cardiovascular diseases, stroke, diabetes, osteoarthritis, cancer, and kidney disease. Studies have shown the anti-inflammation, anti-obesity, and anti-diabetic effects of GDF15, but few have focused on the role of GDF15 in the kidneys.
This study examined the in vivo protective effects of GDF15 in the kidneys of both diet-induced obese mice and GDF15 transgenic mice, as well as investigated whether GDF15 prevents norepinephrine (NE)-induced kidney fibrosis and pro-inflammatory cytokine production in cultured kidney epithelial cells. The in vitro portion of the study included two kidney cell lines, HK-2 and LLC-PK1. Western blot analysis of these cell lines after various treatments of either NE, GDF15, or both revealed some markers of inflammation (NF-kB), fibrosis (a-SMA, TGF-b), and overall kidney injury (NGAL) were significantly greater in cell cultures treated with NE. Higher GDF15 concentrations attenuated the response indicated by NGAL and TNF-a. Kidney tissue samples were analyzed by Western blot, HE staining, and Sirius Red staining. Analysis of wild-type (WT), high-fat diet (WT+HFD), transgenic GDF15 (NAG), and HFD transgenic (NAG+HFD) mice tissues illustrated the reno-protective effects of GDF15. In NAG+HFD mice, the levels of injury markers a-SMA, MMP-2, TIM-1, TNF-a, NF-kB, and TGF-b were not significantly different from the NAG mice, while in WT and WT+HFD mice, a- SMA, MMP-2, TIM-1, NGAL, and TNF-a were significantly different. These results show GDF15 is a possible therapeutic target for kidney injury due to its protective effects in obesity-related kidney disease. Further investigation into GDF15 and its role in the kidneys, as well as other biological processes, is necessary to understand the overall effect of elevated GDF15 levels on the body.
Sullivan, Jessie T., "Reno-protective and Immune Effects of Growth Differentiation Factor 15 in Obesity-related Kidney Disease" (2022). Honors Thesis. 251.