Ms Qinrui Chen1, Prof Carol Pollock1, Dr XinMing Chen1, Dr Qinghua Cao1
1TheUniversityOfSydneyKollingInstitute, Sydney, Australia
Biography:
Daisy (Qinrui) Chen is a first-year PhD student in renal medicine at the University of Sydney, based at the Kolling Institute, Royal North Shore Hospital. She holds a Bachelor of Science (Honours), majoring in Medical Science and Immunology & Pathology. Her research focuses on diabetic and chronic kidney disease (DKD and CKD), with a particular interest in renal fibrosis, mesenchymal stem cells, and the Hippo/YAP1 signaling pathway. Daisy is passionate about translational kidney research and aims to contribute to the development of novel stem cell-based therapies for renal injury and fibrosis.
Background:
Diabetic Kidney Disease (DKD) is a leading cause of kidney failure worldwide. Increasing evidence suggests that DKD damages proximal tubule epithelium, where Yes- associated Protein 1 (YAP1), a key effector of the Hippo pathway, becomes aberrantly activated. YAP1 regulates cell proliferation, survival and fibrosis, yet its role in renal diseases remains unclear. Current DKD therapies are largely ineffective, highlighting the need for novel, targeted interventions.
Aim:
This study investigates the renoprotective role of Mesenchymal stem cell-derived exosomes (MSC-exosomes) on renal proximal tubular cells by targeting YAP1. We aim to determine whether MSC-exosomes can suppress YAP1 activity, reduce inflammation and fibrosis, and rescue renal tubular injury in both in vivo and in vitro.
Methods:
YAP1 localization and activation were examined via immunohistochemistry in folic acid (FA), unilateral ureteral obstruction (UUO) and streptozotocin (STZ) induced-diabetic kidney disease (DKD) mouse models. In vitro, TGF-β1 was used to induce injury in human renal proximal tubular epithelial cells (hRPTECs). YAP1 and fibrotic markers (alpha-Smooth muscle actin, Fibronectin, Collagen I/III/IV) were assessed by qPCR and Western blot. Verteporfin, YAP1-siRNA, and MSC-exosomes were applied to evaluate their effects on YAP1 expression and fibrosis.
Results:
YAP1 was overexpressed and activated in FA, UUO, DN mouse models. In vitro, TGF-β1 induced YAP1 activation in RPTECs. Verteporfin (VP), YAP1-specific siRNA, and MSC-exosomes downregulated YAP1 and fibrotic markers. Notably, both siRNA and MSC-exosomes effectively silenced YAP1 and attenuated TGF-β1-induced fibrotic responses.
Conclusions:
These findings highlight YAP1 as a therapeutic target in renal fibrosis. The inhibitory effects of VP and MSC-exosomes on YAP1 and fibrosis provide mechanistic insight into DKD progression and potential new fibrosis treatment strategies.