促炎性細胞因子增加腎小管細胞中基質囊泡的釋放

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 increase matrix vesicles release from 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 interstitial cells around the thin ascending limb and outward growth to reach the surface of the renal papilla to form a plaque. Histopathological sections showed apatite crystals, extracellular vesicles, and inflammatory cytokines around RP, which were similar to vascular calcification mediated by matrix vesicles (MV). Therefore, we hypothesized that inflammatory cytokines promoted MV release and renal CaP deposition.

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 mineralization and proteins expression. Fourier transform infra red spectrometer (Micro-FTIR) was used to analyze the composition of renal stones. In the in vitro cell experiment, human kidney epithelial cells (HK-2) were treated with TNF-α, IL-1β, TGF-β or BMP-2 for 24 hours and followed with CaCl₂ for 3 hours. The supernatant of culture medium were collated for the test of MV concentration by nanoparticle tracking analysis (NTA).

Results:

In the kidney tissues, it was found that the UUO group showed more calcium phosphate deposition, as well as MV related protein, Annexin II and inflammatory proteins, TNFR1 and TNFR2. In the supernatant from cell culture medium, the concentration of MV were increased after inflammatory cytokines treatment. The composition of renal stones was identified as CaP by Micro-FTIR.

Conclusions:

Inflammation increased MV and renal CaP stone formation. Medication reducing inflammation may be a novel method to decrease MV and CaP stone formation in the kidney.