Thrombospondin‐1 Plays an Essential Role in Hippo Signaling During the Early Phase of Trypanosoma cruzi Infection in Heart Endothelial Cells

• DOI: 10.1096/fasebj.2021.35.s1.04150
• Publication Date: 2021-06-11T01:15:09Z
• Authors: Ashutosh Arun; Kayla Rayford; Ayorinde Cooley; Girish Rachakonda; Fernando Villalta; Siddharth Pratap; Maria Lima; Nader Sheibani; Pius Nde
• Keywords: Chagas Disease; Hippo signaling pathway

Trypanosoma cruzi is an obligate intracellular hemoflagellate parasite which cause Chagas disease. This neglected tropical disease causes severe morbidity and mortality in endemic regions. 30% of chronically infected people suffer from cardiac disorder. heart diseasecan lead to sudden death due arrhythmias or progressive failure. Invasive trypomastigotes released cells can be carried vascular endothelial system infect neighboring distant cells. During the process cellular infection, induces host increase levels thrombospondin-1 (TSP-1) enable infection. TSP-1 plays important roles functioning including with implications cardiovascular health. Hippo signaling components, yes-associated protein 1 (YAP)/transcriptional coactivator PDZ-binding motif (TAZ), are upstream have been linked pathophysiology The molecular mechanisms by T. signals eventually remain unknown. To evaluate importance expression during we challenge prepared Wild Type Knockout mouse (MHEC) invasive at different time points evaluated changes cascade using immunoblotting immunofluorescence assays. We found that turned off hippo pathway TSP-1KO SAV1 MOB1A increased a maximum 2.70±0.23 5.74±1.45 fold 3 6 h, respectively, MHEC compared WT following challenge. was accompanied significant continuous nuclear translocation downstream effector molecule YAP mean fluorescence intensity 10.14±0.40 h wild type Besides this, translocated significantly colocalized transcription co-activator pan-TEAD Pearson's correlation coefficient 0.51±0.06 YAP-Pan-TEAD colocalization MHEC, decreased minimum 0.30±0.01 h. Our finding suggests upregulated essential for regulation early phase These studies advance our understanding Host-Parasite interactions occurring between presence absence TSP-1. Taken together, this further supports concept level induced infection pathogenesis.