促炎性細胞因子增強腎小管細胞中成骨蛋白的表達

林俊廷^1,3、曾一修^1,2

亞東紀念醫院 外科部 創傷科¹與泌尿科²；醫學研究部³

Inflammatory cytokines enhance osteogenic proteins expression in renal tubular cells

Jun-Ting Lin^1,3, Yi-Shiou Tseng^1,2

Divisions of Traumatology¹ and Urology², Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan

Department of Medical Research³, Far Eastern Memorial Hospital, New Taipei City, Taiwan

Purpose:

Randall's plaque (RP) is the deposition of calcium phosphate (CaP) in the renal papilla. However, the mechanism of RP formation is unclear. From the tissue sections of medullary sponge kidney, the osteogenic protein, Runx2 and inflammation were found in renal tissue around RP. The Runx2 had been proven an important osteogenic protein mediating vascular smooth muscle cells to form CaP calcification. We hypothesized that the formation of CaP in the renal cells were mediated by the osteogenic proteins and inflammation.

Materials and Methods:

Unilateral ureteral obstruction (UUO) surgery was performed for male Sprague Dawley rats to create renal inflammation. Male rats were divided into three groups for 8 weeks. The control group received normal diet and sham surgery at 5th week. The high calcium group received high calcium diet and sham surgery at 5^th week. The UUO group received high calcium diet and UUO surgery at 5^th week. The kidneys were harvested at 8^th week to examine stones and proteins expression, and Fourier transform infra red spectrometer (Micro-FTIR) was used to analyze the composition of renal stones. In the in vitro cell experiments, human kidney epithelial cells (HK-2) were given CaCl₂ and TNF-α, IL-1β, TGF-β, BMP-2 for 6 hours. The expression of osteogenic proteins (ALP, OPN, OPG) and inflammatory proteins (TNFR1, TNFR2) were confirmed by western blot.

Results:

The UUO group had the most calcium phosphate deposition in the kidneys, as well as osteogenic proteins OPN, Runx2 and inflammatory proteins TNFR1, TNFR2. In the cell culture, inflammatory cytokines enhance the osteogenic proteins expression including ALP, OPN and OPG. The composition of renal crystals were identified as CaP by Micro-FTIR. 

Conclusions:

Inflammation enhanced osteogenic proteins expression and promoted CaP stone formation in the kidneys. Medication for reducing osteogenic proteins and inflammatory pathway may be a therapeutic strategy for Randall's plaque in the future.