Chronic kidney disease (CKD) is a common illness that is becoming a global public health problem. Tubulointerstitial fibrosis is recognized as a key determinant of progressive CKD due to the strong correlation between the degree of interstitial fibrosis and renal functional loss. Fucoidan is a kind of natural fucose-enriched sulfated polysaccharides found mainly in various species of brown algae and brown seaweed. In recent years, many studies show fucoidan reduces hypoxia nephropathy, and also inhibits liver fibrosis. However, the influence of fucoidan on renal fibrosis is not clear yet. We hypothesized that fucoidan might reduce fibrotic response in renal tubular cells through inhibiting CD44 or Wnt/p-catenin pathways. We study the influence of low-molecular-weight fucoidan (500 Da) on renal fibrosis in vitro with two systems: 1. A pressure-stressed cell model with rat renal tubular cells (NRK-52E). Sixty mmHg of pressure will be applied on NRK-52E cells for different periods. The expression of EMT markers, CD44, Wnts and P-catenin will be monitored by Western blotting. In this model, we can monitor the anti-fibrosis effect of fucoidan at the early stage (before TGF-P up-regulation) of renal fibrosis. 2. A TGF-P-induced fibrosis model with NRK-52E cells. NRK-52E cells are treated with TGF-P to induce fibrotic responses. TGF-P-induced signaling pathways are monitored by Western blotting. In this model, we can monitor the influence of fucoidan on TGF-P-induced of fibrotic responses in NRK-52E cells. Furthermore, we established a unilateral ureteric obstruction (UUO) rat model and a novel mouse CKD model (right nephrectomy with transient ischemic injury to the left kidney) to test the effect of fucoidan on renal function and renal fibrosis. In the present study, we will investigate the influence of low-molecular-weight fucoidan (<500 Da) on renal tubular cell EMT and renal fibrosis in vitro and in vivo. The specific aims of this project are listed as below: 1. To identify the inhibitory effect of fucoidan on pressure-induced renal tubular cell EMT. 2. To identify the inhibitory effect of fucoidan on TGF-P-induced fibrotic signal transduction in NRK-52E cells. 3. To investigate whether the expression levels of CD44 and Wnt/p-catenin are involved in inhibitory effect of fucoidan on renal fibrotic responses. 4. To investigate the influence of fucoidan on renal fibrosis in a UUO model. 5. To investigate the influence of fucoidan on renal function and fibrosis in a CKD model. The investigation the protective effect of fucoidan against renal fibrosis will provides a new therapeutic agent for CKD patients.
|Effective start/end date||8/1/15 → 7/31/16|
- epithelial-mesenchymal transition
- renal tubular cells