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논문분류	춘계학술대회 초록집
제목	Unraveling the Role of YAP/TAZ Signaling in Kidney Fibrosis
저자	Seunghyeok Choi
출판정보	2024; 2024(1):
키워드
초록	Patients suffering from chronic kidney disease (CKD) increased followed by increased metabolic disease. CKD, which has various complications, becomes the significant burden on public health. Renal fibrosis is the final and common pathway in the development and progression of CKD regardless of etiology. Excessive production and accumulation of extracellular matrix (ECM) and epithelial-mesenchymal transformation (EMT) paly an important role in pathogenesis of renal fibrosis. The Hippo pathway, first discovered in drosophila melanogaster, is evolutionally conserved cascade the regulates cell proliferation, organ size, and regeneration. YAP/TAZ, which is the final effector of the Hippo pathway, cause pro-fibrogenic signals. YAP/TAZ activation is linked to fibrosis of kidney. There have been several reports regarding the role of YAP/TAZ in renal pathology. YAP/TAZ have several roles in distinguished cells in context dependent manners. YAP/TAZ acts as an antiapoptotic protein for podocyte. Nuclear YAP was observed in injured podocyte during cell proliferation and repair. In contrast, prolonged activation of YAP was related to renal fibrosis. For tubular epithelial cells, upregulated YAP in UUO model was related to excessive accumulation of ECM and progressive organ fibrosis. YAP activation also increased EMT phenotype change in UUO model which led to TGF-β/Smad signaling pathway activation. Chemical inhibition of YAP through Verteporfin attenuated renal tubulointerstitial fibrosis in UUO model. Hyperglycemic stimulus on mesangial cell, which activates YAP/TAZ, dedifferentiated mesangial cell to myelofibroblast and increased the ECM deposition. Hyperactivation of YAP/TAZ in mesangial cell finally induced glomerular fibrosis. YAP/TAZ, the final effector of the Hippo pathway, are involved in renal fibrosis by acting in various stimulation in each cell of kidney. However, as mentioned in the script, YAP/TAZ have diverse roles in individual cells by the context dependent manners. To target the YAP/TAZ for therapeutic purpose, precise control of YAP/TAZ in distinguished cells in accurate time point should be ensured.
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