Type 1 Diabetes (T1D) is a challenging autoimmune disease that affects 1 in 10 adults in the United States. It is a lifelong condition caused by T-cell infiltration-induced β-cell apoptosis in islets within the pancreas. Hepatocyte growth factor (HGF)/c-Met signaling is responsible for the activation of transcription factors for cell survival, proliferation and metastasis. It also correlates with increased amounts of myeloidderived suppressor cells (MDSCs), which inhibit cytotoxic T-cell activation. Therefore, in individuals with T1D, c-Met plays a crucial role in β-cell survival. To further understand the relationship between HGF/c-Met signaling and the onset of T1D in vivo and in vitro, my study quantified HGF and c-Met at various stages of mice’s growth. I extracted islets and immune cells from nonobese diabetic (NOD) mice pancreas and lymph nodes, respectively. I then conducted immunohistochemistry, quantitative polymerase chain reactions (qPCRs) and flow cytometry to quantify HGF and c-Met receptors in relation to islet inflammation and age. I report that c-Met concentration increases as insulitis caused by T-cell infiltration increases. Additionally, there is an inversely proportional relationship between T1D onset and HGF/cMet signaling. Although it is not clear if c-Met is a driving factor or a response caused by T1D, a clear understanding of the HGF/cMet signaling pathway could further the development of more therapies for individuals with T1D.

References

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