A small-molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase improves obesity, nephropathy and cardiomyopathy in obese ZSF1 rats.

Prolyl hydroxylase (PH) enzymes control the degradation of hypoxia-inducible factor (HIF), a transcription factor known to regulate erythropoiesis, angiogenesis, glucose metabolism, cell proliferation, and apoptosis. HIF-PH inhibitors (HIF-PHIs) correct anemia in patients with renal disease and in animal models of anemia and kidney disease. However, the effects of HIF-PHIs on comorbidities associated with kidney disease remain largely unknown.

THE USE OF LOW-DOSE CT WITH ADAPTIVE STATISTICAL ITERATIVE RECONSTRUCTION FOR THE DIAGNOSIS OF URINARY CALCULI.

This study aimed to explore the diagnosis of urinary calculi through utilisation of low-dose computed tomography (LDCT) with adaptive statistical iterative reconstruction (ASIR). Data from 140 patients that had undergone pathological or operative diagnosis with urinary calculi were analysed. Patients were divided into two groups based on whether they received conventional-dose computed tomography (CDCT) or LDCT, respectively, followed by filtered back projection or ASIR.

Nonclinical Characterization of the Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat, a Novel Treatment of Anemia of Chronic Kidney Disease.

Anemia of chronic kidney disease (CKD) is a multifactorial disorder caused by impaired erythropoietin (EPO) production and altered iron homeostasis associated with inflammation. Hypoxia-inducible factor (HIF) is a transcription factor that stimulates erythropoiesis via a coordinated response involving increased EPO production and enhanced iron availability for Hb synthesis. HIF degradation is regulated by HIF-prolyl hydroxylase (HIF-PH) enzymes.

Cooperative interaction of CTGF and TGF-β in animal models of fibrotic disease.

Background: Connective tissue growth factor (CTGF) is widely thought to promote the development of fibrosis in collaboration with transforming growth factor (TGF)-β; however, most of the evidence for its involvement comes from correlative and culture-based studies. In this study, the importance of CTGF in tissue fibrosis was directly examined in three murine models of fibrotic disease: a novel model of multiorgan fibrosis induced by repeated intraperitoneal injections of CTGF and TGF-β2; the unilateral ureteral obstruction (UUO) renal fibrosis model; and an intratracheal bleomycin instillation model of pulmonary fibrosis.

Results: Intraperitoneal coadministration of CTGF and TGF-β2 elicited a profound fibrotic response that was inhibited by the human anti-CTGF antibody FG-3019, as indicated by the ability of FG-3019 to ameliorate the histologic signs of fibrosis and reduce the otherwise increased hydroxyproline:proline (Hyp:Pro) ratios by 25% in kidney (P < 0.

ACE inhibition increases expression of the ETB receptor in kidneys of mice with unilateral obstruction.

Unilateral ureteral obstruction (UUO) is a well-established model for the study of interstitial fibrosis in the kidney. It has been shown that the renin-angiotensin system plays a central role in the progression of interstitial fibrosis. Recent studies indicate that endothelin, a powerful vasoconstrictive peptide, may play an important role in some types of renal disease.

Transforming growth factor-beta induces renal epithelial jagged-1 expression in fibrotic disease.

For elucidation of the mechanisms by which growth factors and cytokines affect renal epithelial cells, gene array analysis of renal cells cultured in the presence of transforming growth factor-beta1 (TGF-beta1) was performed. Many genes that were not previously considered to be involved in renal cell biologic processes were affected, one of which was jagged-1. The jagged ligand/notch receptor family controls the formation of boundaries between groups of cells and regulates cell fates.

Bone morphogenetic protein-7 improves renal fibrosis and accelerates the return of renal function.

A prevention protocol has demonstrated that bone morphogenetic protein-7 (BMP-7) blunted the development of fibrosis in a rat model of unilateral ureteral obstruction. This prevention protocol also preserved, to an extent, renal function. The prevention protocol was extended and a treatment protocol used to examine if BMP-7 was beneficial at limiting fibrosis of the kidney when the BMP-7 was administered during the progression of fibrotic disease.

Induction of CD14 in tubular epithelial cells during kidney disease.

Analysis of gene expression in a mouse model of unilateral ureteral obstruction (UUO) revealed significant induction of CD14 mRNA in kidneys with obstructed ureters. Immunocytochemical analysis indicated that CD14 was upregulated in tubular epithelial cells and this upregulation was not attributable to infiltration of the kidneys by mononuclear cells. This induction of CD14 mRNA was found to occur in BALB/C, C57BL/6, C3H/HeN, and C3H/HeJ mice during UUO.