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Dive into the research topics where Rui Xi Li is active.

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Featured researches published by Rui Xi Li.


Kidney International | 2013

The TLR4 antagonist CRX-526 protects against advanced diabetic nephropathy

Miao Lin; Wai Han Yiu; Rui Xi Li; Hao Jia Wu; Dickson W.L. Wong; Loretta Y.Y. Chan; Joseph C.K. Leung; Kar Neng Lai; Sydney C.W. Tang

We recently showed that Toll-like receptor (TLR) TLR4 was overexpressed in the human diabetic kidney, which could promote tubular inflammation. Here we explored whether the TLR4 antagonist, CRX-526, has therapeutic potential to attenuate renal injuries and slow the progression of advanced diabetic nephropathy in wild-type and endothelial nitric oxide synthase (eNOS) knockout mice. In the latter, the endogenous TLR4 ligand, high-mobility group box 1, was upregulated more than in wild-type animals. Four weeks after streptozotocin induction of diabetes, mice were injected with either CRX-526 or vehicle for 8 weeks. CRX-526 significantly reduced albuminuria and blood urea nitrogen without altering blood glucose and systolic blood pressure in diabetic mice. Glomerular hypertrophy, glomerulosclerosis, and tubulointerstitial injury were attenuated by CRX-526, which was associated with decreased chemokine (C-C motif) ligand (CCL)-2, osteopontin, CCL-5 overexpression, subsequent macrophage infiltration, and collagen deposition. These effects were associated with inhibition of TGF-β overexpression and NF-κB activation. In vitro, CRX-526 inhibited high glucose-induced osteopontin upregulation and NF-κB nuclear translocation in cultured human proximal tubular epithelial cells. Thus, we provided evidence that inhibition of TLR4 with the synthetic antagonist CRX-526 conferred renoprotective effects in eNOS knockout diabetic mice with advanced diabetic nephropathy.


Frontiers in Physiology | 2015

Role of bone morphogenetic protein-7 in renal fibrosis

Rui Xi Li; Wai Han Yiu; Sydney C.W. Tang

Renal fibrosis is final common pathway of end stage renal disease. Irrespective of the primary cause, renal fibrogenesis is a dynamic process which involves a large network of cellular and molecular interaction, including pro-inflammatory cell infiltration and activation, matrix-producing cell accumulation and activation, and secretion of profibrogenic factors that modulate extracellular matrix (ECM) formation and cell-cell interaction. Bone morphogenetic protein-7 is a protein of the TGF-β super family and increasingly regarded as a counteracting molecule against TGF-β. A large variety of evidence shows an anti-fibrotic role of BMP-7 in chronic kidney disease, and this effect is largely mediated via counterbalancing the profibrotic effect of TGF-β. Besides, BMP-7 reduced ECM formation by inactivating matrix-producing cells and promoting mesenchymal-to-epithelial transition (MET). BMP-7 also increased ECM degradation. Despite these observations, the anti-fibrotic effect of BMP-7 is still controversial such that fine regulation of BMP-7 expression in vivo might be a great challenge for its ultimate clinical application.


PLOS ONE | 2014

Mesenchymal Stem Cells Modulate Albumin-Induced Renal Tubular Inflammation and Fibrosis

Hao Jia Wu; Wai Han Yiu; Rui Xi Li; Dickson W.L. Wong; Joseph C.K. Leung; Loretta Y.Y. Chan; Yuelin Zhang; Qizhou Lian; Miao Lin; Hung-Fat Tse; Kar Neng Lai; Sydney C.W. Tang

Bone marrow-derived mesenchymal stem cells (BM-MSCs) have recently shown promise as a therapeutic tool in various types of chronic kidney disease (CKD) models. However, the mechanism of action is incompletely understood. As renal prognosis in CKD is largely determined by the degree of renal tubular injury that correlates with residual proteinuria, we hypothesized that BM-MSCs may exert modulatory effects on renal tubular inflammation and epithelial-to-mesenchymal transition (EMT) under a protein-overloaded milieu. Using a co-culture model of human proximal tubular epithelial cells (PTECs) and BM-MSCs, we showed that concomitant stimulation of BM-MSCs by albumin excess was a prerequisite for them to attenuate albumin-induced IL-6, IL-8, TNF-α, CCL-2, CCL-5 overexpression in PTECs, which was partly mediated via deactivation of tubular NF-κB signaling. In addition, albumin induced tubular EMT, as shown by E-cadherin loss and α-SMA, FN and collagen IV overexpression, was also prevented by BM-MSC co-culture. Albumin-overloaded BM-MSCs per se retained their tri-lineage differentiation capacity and overexpressed hepatocyte growth factor (HGF) and TNFα-stimulating gene (TSG)-6 via P38 and NF-κB signaling. Albumin-induced tubular CCL-2, CCL-5 and TNF-α overexpression were suppressed by recombinant HGF treatment, while the upregulation of α-SMA, FN and collagen IV was attenuated by recombinant TSG-6. Neutralizing HGF and TSG-6 abolished the anti-inflammatory and anti-EMT effects of BM-MSC co-culture in albumin-induced PTECs, respectively. In vivo, albumin-overloaded mice treated with mouse BM-MSCs had markedly reduced BUN, tubular CCL-2 and CCL-5 expression, α-SMA and collagen IV accumulation independent of changes in proteinuria. These data suggest anti-inflammatory and anti-fibrotic roles of BM-MSCs on renal tubular cells under a protein overloaded condition, probably mediated via the paracrine action of HGF and TSG-6.


Clinical Science | 2015

BMP7 reduces inflammation and oxidative stress in diabetic tubulopathy

Rui Xi Li; Wai Han Yiu; Hao Jia Wu; Dickson W.L. Wong; Loretta Y.Y. Chan; Miao Lin; Joseph C.K. Leung; Kar Neng Lai; Sydney C.W. Tang

Bone morphogenetic protein 7 (BMP7) has been reported to confer renoprotective effects in acute and chronic kidney disease models, but its potential role in Type 2 diabetic nephropathy remains unknown. In cultured human proximal tubular epithelial cells (PTECs), exposure to advanced glycation end-products (AGEs) induced overexpression of intercellular adhesion molecule 1 (ICAM1), monocyte chemoattractant protein 1 (MCP1), interleukin 8 (IL-8) and interleukin 6 (IL-6), involving activation of p44/42 and p38 mitogen-activated protein kinase (MAPK) signalling. BMP7 dose-dependently attenuated AGE-induced up-regulation of ICAM1, MCP1, IL-8 and IL-6 at both mRNA and protein levels. Moreover, BMP7 suppressed AGE-induced p38 and p44/42 MAPK phosphorylation and reactive oxygen species production in PTECs. Compared with vehicle control, uninephrectomized db/db mice treated with BMP7 for 8 weeks had significantly lower urinary albumin-to-creatinine ratio (3549±816.2 μg/mg compared with 8612±2037 μg/mg, P=0.036), blood urea nitrogen (33.26±1.09 mg/dl compared with 37.49±0.89 mg/dl, P=0.006), and renal cortical expression of ICAM1 and MCP1 at both gene and protein levels. In addition, BMP7-treated animals had significantly less severe tubular damage, interstitial inflammatory cell infiltration, renal cortical p38 and p44/42 phosphorylation and lipid peroxidation. Our results demonstrate that BMP7 attenuates tubular pro-inflammatory responses in diabetic kidney disease by suppressing oxidative stress and multiple inflammatory signalling pathways including p38 and p44/42 MAPK. Its potential application as a therapeutic molecule in diabetic nephropathy warrants further investigation.


Nephrology Dialysis Transplantation | 2018

Complement C5a inhibition moderates lipid metabolism and reduces tubulointerstitial fibrosis in diabetic nephropathy

Wai Han Yiu; Rui Xi Li; Dickson W.L. Wong; Hao Jia Wu; Kam Wa Chan; Loretta Y.Y. Chan; Joseph C.K. Leung; Kar Neng Lai; Steven H. Sacks; Wuding Zhou; Sydney C.W. Tang

Background Complement C5 mediates pro-inflammatory responses in many immune-related renal diseases. Given that the C5a level is elevated in diabetes, we investigated whether activation of C5a/C5aR signalling plays a pathogenic role in diabetic nephropathy (DN) and the therapeutic potential of C5a inhibition for renal fibrosis. Methods Human renal biopsies from patients with DN and control subjects were used for immunohistochemical staining of complement C5 components. Renal function and tubulointerstitial injury were compared between db/m mice, vehicle-treated mice and C5a inhibitor-treated db/db mice. A cell culture model of tubule epithelial cells (HK-2) was used to demonstrate the effect of C5a on the renal fibrotic pathway. Results Increased levels of C5a, but not of its receptor C5aR, were detected in renal tubules from patients with DN. The intensity of C5a staining was positively correlated with the progression of the disease. In db/db mice, administration of a novel C5a inhibitor, NOX-D21, reduced the serum triglyceride level and attenuated the upregulation of diacylglycerolacyltransferase-1 and sterol-regulatory element binding protein-1 expression and lipid accumulation in diabetic kidney. NOX-D21-treated diabetic mice also had reduced serum blood urea nitrogen and creatinine levels with less glomerular and tubulointerstitial damage. Renal transforming growth factor beta 1 (TGF-β1), fibronectin and collagen type I expressions were reduced by NOX-D21. In HK-2 cells, C5a stimulated TGF-β production through the activation of the PI3K/Akt signalling pathway. Conclusions Blockade of C5a signalling by NOX-D21 moderates altered lipid metabolism in diabetes and improved tubulointerstitial fibrosis by reduction of lipid accumulation and TGF-β-driven fibrosis in diabetic kidney.


Oncotarget | 2017

Human induced pluripotent stem cell-derived mesenchymal stem cells prevent adriamycin nephropathy in mice

Hao Jia Wu; Wai Han Yiu; Dickson W.L. Wong; Rui Xi Li; Loretta Y.Y. Chan; Joseph C.K. Leung; Yuelin Zhang; Qizhou Lian; Kar Neng Lai; Hung-Fat Tse; Sydney C.W. Tang

Human induced pluripotent stem cell-derived mesenchymal stem cells (iPS-MSCs) are emerging as attractive options for use in cell replacement therapy, but their effect in kidney diseases remains unknown. Here, we showed that intravenous injection of iPS-MSCs protect against renal function loss in both short-term and long-term models of adriamycin nephropathy (AN). In the short-term AN model, iPS-MSCs conferred a substantial anti-apoptotic effect on tubular cells, associated with a downregulation of Bax and Bax/Bcl2 ratio and an upregulation of survivin expression. In vitro, conditioned medium from iPS-MSCs (iPSMSC-CM) significantly limited albumin-induced tubular apoptosis and enhanced tubular proliferation, accompanied by a reduced expression of tubular Bax and an elevated expression of Bcl2 and survivin. Oxidative stress was markedly attenuated by iPS-MSCs both in AN mice and in protein-overloaded tubular cells. In the long-term AN model, repeated injections of iPS-MSCs significantly inhibited tubulointerstitial fibrosis and reduced intrarenal deposition of collagen I, collagen IV and αSMA. Modulation of the hedgehog signaling pathway contributed to the anti-fibrotic effect of iPS-MSCs in chronic AN. Finally, we detected that most of the infused iPS-MSCs were entrapped in the lungs. In conclusion, our data support a beneficial role of iPS-MSCs in both acute and chronic AN.


Kidney International | 2016

Kallistatin protects against diabetic nephropathy in db/db mice by suppressing AGE-RAGE-induced oxidative stress.

Wai Han Yiu; Dickson W.L. Wong; Hao Jia Wu; Rui Xi Li; Irene Yam; Loretta Y.Y. Chan; Joseph C.K. Leung; Hui Y. Lan; Kar Neng Lai; Sydney C.W. Tang


Archive | 2013

Role of bone morphogenetic protein-7 (BMP7) in diabetic tubulopathy

Rui Xi Li; Wai Han Yiu; Hao Jia Wu; Miao Lin; Dwl Wong; Lyy Chan; Jck Leung; Kn Lai; Scw Tang


Archive | 2015

Inhibition of miR-34a reduces podocyte apoptosis by targeting Bcl-2 and autophagy

Y Liu; Rui Xi Li; Wai Han Yiu; Hao Jia Wu; Wld Wong; Jck Leung; Ly Chan; Kn Lai; M Saleem; Pw Mathieson; Scw Tang


Archive | 2014

BMP7 reduces tubular inflammation and oxidative stress in diabetic nephropathy

Rui Xi Li; Wai Han Yiu; Hao Jia Wu; Dwl Wong; Lyy Chan; Miao Lin; Jck Leung; Kn Lai; Scw Tang

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Wai Han Yiu

University of Hong Kong

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Hao Jia Wu

University of Hong Kong

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Kar Neng Lai

University of Hong Kong

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Miao Lin

University of Hong Kong

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Jck Leung

University of Hong Kong

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Scw Tang

University of Hong Kong

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