Osteopontin (Opn) and polyoma enhancer-binding protein (PEBP) 2αA/core binding factor (CBFA) 1 have been suggested to play important roles in ossification. The overlapping localization of opn and PEBP2αA/CBFA1 mRNA, and the marked decrease of opn mRNA expression in PEBP2αA knockout mice, indicated that the transcription of opn gene was controlled by PEBP2αA. In the present study, we determined the direct regulation of PEBP2αA on the opn promoter activity. Opn promoter activity was markedly enhanced by PEBP2αA and ETS1 in a synergistic manner. The synergistic effect was diminished when either the PEBP2αA or ETS1 binding site was mutated, or the spatial arrangement of these sites was mutated by a 4-nt insertion. The distance between these sites was important for transactivation but not protein-DNA binding. The direct interaction between PEBP2αA and ETS1 was depended on protein-DNA binding. These results suggested that the specific spatial arrangement of both sites and direct interaction between PEBP2αA and ETS1, were essential for promoter function. Furthermore, endogenous opn mRNA was decreased with the introduction of dominant negative PEBP2αA to MC3T3/E1 cells expressing endogenous PEBP2αA, ETS1 and opn. These findings suggest that PEBP2αA and ETS1 cooperate in vivo to regulate expression of the opn gene in the skeletal tissue. Cell type-specific regulation of Opn gene expression will also be discussed.

Randall plaques (RPs) can contribute to the formation of idiopathic calcium oxalate (CaOx) kidney stones; however, genes related to RP formation have not been identified. We previously reported the potential therapeutic role of osteopontin (OPN) and macrophages in CaOx kidney stone formation, discovered using genome-recombined mice and genome-wide analyses. Here, to characterize the genetic pathogenesis of RPs, we used microarrays and immunohistology to compare gene expression among renal papillary RP and non-RP tissues of 23 CaOx stone formers (SFs) (age- and sex-matched) and normal papillary tissue of seven controls. Transmission electron microscopy showed OPN and collagen expression inside and around RPs, respectively. Cluster analysis revealed that the papillary gene expression of CaOx SFs differed significantly from that of controls. Disease and function analysis of gene expression revealed activation of cellular hyperpolarization, reproductive development, and molecular transport in papillary tissue from RPs and non-RP regions of CaOx SFs. Compared with non-RP tissue, RP tissue showed upregulation (˃2-fold) of LCN2, IL11, PTGS1, GPX3, and MMD and downregulation (0.5-fold) of SLC12A1 and NALCN (P<0.01). In network and toxicity analyses, these genes associated with activated mitogen-activated protein kinase, the Akt/phosphatidylinositol 3-kinase pathway, and proinflammatory cytokines that cause renal injury and oxidative stress. Additionally, expression of proinflammatory cytokines, numbers of immune cells, and cellular apoptosis increased in RP tissue. This study establishes an association between genes related to renal dysfunction, proinflammation, oxidative stress, and ion transport and RP development in CaOx SFs.

Purpose: Urinary stones are similar to arteriosclerosis in epidemiology, mechanism, calcification composition and age at frequent occurrence. The calcification that occurs in arterioscleros...

Background and Purpose: Percutaneous nephrolithotomy (PCNL) is considered the standard procedure for the removal of large renal calculi. The development of the “minimally invasive PCNL” (mini-PCNL) has reduced the complications of the surgery; it also appears to be associated with less morbidity than the conventional PCNL (con-PCNL). This study aimed at evaluating the efficacy of endoscopic intrarenal surgery, using the prone-split leg position, using flexible ureteroscopy and mini-PCNL (mini- endoscopic combined intrarenal surgery [ECIRS]) by retrospectively comparing this technique with mini-PCNL and con-PCNL. Patients and Methods: In total, 161 consecutive patients who were observed for the follow-up of large renal calculi between February 2004 and January 2013 were selected for mini-ECIRS (60), mini-PCNL (19), or con-PCNL (82). Mini-ECIRS was performed with patients in the prone split-leg position via 18F minipercutaneous tract and 14F ureteral access sheath. The mini-PCNL was performed via 18F percutaneous tract and con-PCNL performed via the 30F tract. Mean size of the renal calculi removed via mini-ECIRS, mini-PCNL, and con-PCNL were 39.2, 38.4, and 34.6 mm, respectively. Results: Average surgical time for mini-ECIRS was shorter than that for mini-PCNL and con-PCNL (120.5 vs 181.9 vs 134.1 min, respectively; P <0.001). The stone-free rate for mini-ECIRS was significantly higher than that of the other procedures (initial rates 81.7% vs 38.9% vs 45.1%, respectively; P <0.001; rates after further treatment 86.7% vs 61.1% vs 61.0%, respectively; P =0.002). Only one patient in the mini-ECIRS group needed blood transfusions. The decrease in hemoglobin during mini-ECIRS and mini-PCNL was significantly lower than that during con-PCNL ( P =0.011). Conclusion: Mini-ECIRS is better than monotherapy with mini-PCNL or con-PCNL. The study results show that mini-ECIRS is a safe, efficient, and versatile procedure that can be effective for the management of renal calculi.

In our previous report, M2-macrophage (Mφs) deficient mice showed increased renal calcium oxalate (CaOx) crystal formation; however, the role of Mφs-related-cytokines and chemokines that affect kidney stone formation remains unknown. Here, we investigated the role of M1/M2s in crystal development by using in vitro and in vivo approaches. The crystal phagocytic rate of bone marrow-derived M2Mφs was higher than that of bone marrow-derived Mφs and M1Mφs and increased on co-culture with renal tubular cells (RTCs). However, the amount of crystal attachment on RTCs reduced on co-culture with M2Mφs. In six hyperoxaluric C57BL/6J mice, M1Mφ transfusion and induction by LPS and IFN-γ facilitated renal crystal formation, whereas M2Mφ transfusion and induction by IL-4 and IL-13 suppressed renal crystal formation compared with the control. These M2Mφ treatments reduced the expression of crystal-related genes, such as osteopontin and CD44, whereas M1Mφ treatment increased the expression of pro-inflammatory and adhesion-related genes such as IL-6, inducible NOS, TNF-α, C3, and VCAM-1. The expression of M2Mφ-related genes was lower whereas that of M1Mφ-related genes was higher in papillary tissue of CaOx stone formers. Overall, our results suggest that renal crystal development is facilitated by M1Mφs, but suppressed by M2Mφs.