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Background: Endothelial cells are known to contribute to kidney fibrosis via endothelial-mesenchymal transition (EndoMT). Matrix metalloproteinase 9 (MMP-9) is known to be profibrotic. However, whether MMP-9 contributes to kidney fibrosis via EndoMT is unknown. Methods: Primary mouse renal peritubular endothelial cells (MRPECs) were isolated and treated by recombinant human transforming growth factor beta 1 (rhTGF-β1) with or without MMP-9 inhibitor or by recombinant human MMP-9 (rhMMP- 9) alone. Kidney fibrosis was induced by unilateral ureteral obstruction (UUO) in MMP-9 knockout (KO) and wide-type (WT) control mice. The effects of MMP-9 on EndoMT of MRPECs and kidney fibrosis were examined. Results: We showed that MRPECs underwent EndoMT after rhTGF-β1 treatment or in UUO kidney as evidenced by decreased expression of endothelial markers, vascular endothelial cadherin (VE-cadherin) and CD31, and increased levels of mesenchymal markers, a-smooth muscle actin (a-SMA) and vimentin. The expression of fibrosis markers was also upregulated significantly after rhTGF-β1 treatment in MRPECs. The EndoMT and fibrosis markers were significantly less in rhTGF-β1-treated MMP-9 KO MRPECs, whereas MMP-9 alone was sufficient to induce EndoMT in MRPECs. UUO kidney ofMMP-9 KO mice showed significantly less interstitial fibrosis and EndoMT in MRPECs. Notch signaling shown by Notch intracellular domain (NICD) was increased, while Notch-1 was decreased in rhTGF-β1-treated MRPECs of MMP-9WT but notMMP-9 KO mice. Inhibition ofMMP-9 or Notch signaling prevented rhTGF-β1- or rhMMP-9-induced a-SMA and NICD upregulation in MRPECs. UUO kidney of MMP-9 KOmice had less staining of Notch signaling transcription factor Hey-1 in VE-cadherin-positive MRPECs than WT controls. Conclusions: Our results demonstrate that MMP-9-dependent Notch signaling plays an important role in kidney fibrosis through EndoMT ofMRPECs. [ABSTRACT FROM AUTHOR]

Ultrasound examination is a non-invasive diagnostic technique that is used on patients with suspected or established renal disease. The purpose of this study was to determine the role of intrarenal Doppler ultrasonography in the assessment of the renal pathology of patients with chronic kidney disease (CKD), as shown by kidney biopsy. This retrospective analysis enrolled 992 consecutive patients with CKD who underwent intrarenal Doppler ultrasonography and a kidney biopsy at the Departments of Nephrology of three hospitals between January 2006 and December 2010. Doppler parameters, including the peak systolic velocity (PSV), end-diastolic velocity and resistive index (RI) of the interlobar arteries, were compared with the renal biopsy findings. The RI of the interlobar arteries was correlated with the estimated glomerular filtration rate and the histological damage scores, demonstrating the most evident correlation with the tubulointerstitial damage (TI) score among the three histological components. The PSV of the interlobar arteries increased as the CKD stage progressed and correlated with a number of the renal histological changes, including the glomerulosclerosis and TI scores. The RI and PSV of the interlobar artery are correlated with the histopathological pattern in CKD. Thus, the RI and PSV of the interlobar artery may be potential indicators for monitoring the progression of renal damage. [ABSTRACT FROM AUTHOR]