下大静脈及び腸骨静脈血栓を伴った後腹膜線維症の1例

53歳女.両下肢の腫脹と乏尿を主訴に当院受診, CT上両側水腎症と両側腸骨動脈を取り囲む辺縁不整な軟部組織陰影を認めた, 腎後性腎不全に対し両側ダブルJカテーテル留置, 造影CTにて下大静脈及び左腸骨静脈内に血栓を認め, また下大静脈造影及びMRアンジオグラフィー(MRA)にて左腸骨静脈閉塞を認めた.中心静脈血栓を伴う特発性後腹膜線維症と診断し, 経口よりプレドニゾロン及びワーファリン投与開始した.投与1ヵ月後のCT及びMRAで血栓の消失を認め, 水腎症は改善, 再発を認めていないA 53-year-old female was hospitalized for evaluation of swelling in the bilateral lower extremities. A computed tomography (CT) scan of the abdomen revealed bilateral hydronephrosis and features consistent with retroperitoneal fibrosis. Transfemoral venography and magnetic resonance angiography (MRA) showed thrombosis of both the left common iliac vein and inferior vena cava, and filling of numerous collateral veins in the retroperitoneal area. A diagnosis of idiopathic retroperitoneal fibrosis with central venous thrombosis was made. Ureteral stenting, medication with corticosteroids and subsequent warfarin were started, resulting in marked improvement of renal function and the lower extremities. Diagnosis and follow-up of deep venous thrombosis can be aided by MRA. Administration of steroids with anticoagulation was considered to be successful in the case presenting with deep venous thrombosis caused by retroperitoneal fibrosis

Correction: Adipose Tissue-Derived Mesenchymal Stem Cells in Long-Term Dialysis Patients Display Downregulation of PCAF Expression and Poor Angiogenesis Activation.

[This corrects the article DOI: 10.1371/journal.pone.0102311.]

Adipose tissue-derived mesenchymal stem cells in long-term dialysis patients display downregulation of PCAF expression and poor angiogenesis activation.

We previously demonstrated that mesenchymal stem cells (MSCs) differentiate into functional kidney cells capable of urine and erythropoietin production, indicating that they may be used for kidney regeneration. However, the viability of MSCs from dialysis patients may be affected under uremic conditions. In this study, we isolated MSCs from the adipose tissues of end-stage kidney disease (ESKD) patients undergoing long-term dialysis (KD-MSCs; mean: 72.3 months) and from healthy controls (HC-MSCs) to compare their viability. KD-MSCs and HC-MSCs were assessed for their proliferation potential, senescence, and differentiation capacities into adipocytes, osteoblasts, and chondrocytes. Gene expression of stem cell-specific transcription factors was analyzed by PCR array and confirmed by western blot analysis at the protein level. No significant differences of proliferation potential, senescence, or differentiation capacity were observed between KD-MSCs and HC-MSCs. However, gene and protein expression of p300/CBP-associated factor (PCAF) was significantly suppressed in KD-MSCs. Because PCAF is a histone acetyltransferase that mediates regulation of hypoxia-inducible factor-1α (HIF-1α), we examined the hypoxic response in MSCs. HC-MSCs but not KD-MSCs showed upregulation of PCAF protein expression under hypoxia. Similarly, HIF-1α and vascular endothelial growth factor (VEGF) expression did not increase under hypoxia in KD-MSCs but did so in HC-MSCs. Additionally, a directed in vivo angiogenesis assay revealed a decrease in angiogenesis activation of KD-MSCs. In conclusion, long-term uremia leads to persistent and systematic downregulation of PCAF gene and protein expression and poor angiogenesis activation of MSCs from patients with ESKD. Furthermore, PCAF, HIF-1α, and VEGF expression were not upregulated by hypoxic stimulation of KD-MSCs. These results suggest that the hypoxic response may be blunted in MSCs from ESKD patients

Differences in mRNA expression between KD-MSCs and HC-MSCs by RT-PCR analysis.

<p>*p<0.05 between HC-MSCs (n = 6) and KD-MSCs (n = 9).</p

Proliferation and senescence of HC-MSCs and KD-MSCs.

<p>(A) Representative images of HC-MSCs and KD-MSCs (magnification, ×40). Left columns show assessment of senescence using the senescence biomarker SA-β-gal (green) in HC-MSCs and KD-MSCs. Black scale bars represent 50 µm. Right columns show DAPI staining of senescence-associated heterochromatic foci (SAHF) in MSC DNA foci. White scale bars represent 10 µm. Insets show an enlargement of DAPI staining (white scale bars represent 5 µm). Early passage: P5; late passage: P10. (B) Quantitative assessment of SA-β-gal positive cells. Data are the mean ± SE (<i>n</i> = 4). ^*<i>P</i><0.05. (C) Cumulative population doublings (PDs) of HC-MSCs (<i>n</i> = 5) and KD-MSCs (<i>n</i> = 5) from passage 5–10. Data are expressed as the mean ± SE. ^*<i>P</i><0.05. Experiments were performed in triplicate.</p

Differentiation capacities of HC-MSCs and KD-MSCs.

<p>(A) Adipogenic differentiation of HC-MSCs (top and left) and KD-MSCs (top and right) was examined after 2 weeks of culture under adipogenic conditions by Sudan III staining (original magnification, ×100). Osteogenic differentiation of HC-MSCs (second from top and left) and KD-MSCs (second from top and right) was examined after 4 weeks of culture under osteogenic conditions by von Kossa staining (original magnification, ×100). Chondrogenic differentiation of HC-MSCs (bottom and left) and KD-MSCs (bottom and right) was examined after 3 weeks of culture under chondrogenic conditions by Safranin O/Fast green staining (original magnification, ×100). (B) GPDH activity of cells was measured to compare the adipogenic differentiation capacities of HC-MSCs (<i>n</i> = 5) and KD-MSCs (<i>n</i> = 5). Data are expressed as the mean ± standard error (SE). ^*<i>P</i><0.05. (C) ALP activity of the cells was measured to indicate their osteogenic differentiation capacity (<i>n</i> = 4). Data are expressed as the mean ± SE. ^*<i>P</i><0.05.</p

Real-time PCR array, quantitative PCR, and western blot analyses of MSCs.

<p>(A) Downregulation of multiple stem cell-relevant transcription factors in KD-MSCs (<i>n</i> = 9) compared with HC-MSCs (<i>n</i> = 6). The fold change [2∧(−ΔΔCt)] is the normalized gene expression [2∧(−ΔCt)] in KD-MSCs relative to that in HC-MSCs. <i>P</i>-values were calculated based on the Student's <i>t</i>-test of replicate 2∧(−ΔCt) values for each gene in HC-MSCs and KD-MSCs. <i>P</i><0.05 is indicated with black arrows. (B) Quantitative PCR was performed to measure the levels of gene expression in HC-MSCs (<i>n</i> = 6) and KD-MSCs (<i>n</i> = 6). Data are expressed as the mean ± SE. ^*<i>P</i><0.05. (C) Western blot analysis of PCAF in KD-MSCs and HC-MSCs. PCAF expression was decreased in KD-MSCs (<i>n</i> = 9) compared with HC-MSCs (<i>n</i> = 6). PCAF protein levels are expressed relative to β-actin. Data are expressed as the mean ± SE. ^*<i>P</i><0.05.</p