Primary cilia regulate the osmotic stress response of renal epithelial cells through TRPM3
Primary cilia sense environmental conditions, including osmolality, but whether cilia participate in the osmotic response in renal epithelial cells is not known. The transient receptor potential (TRP) channels TRPV4 and TRPM3 are osmoresponsive. TRPV4 localizes to cilia in certain cell types, while renal subcellular localization of TRPM3 is not known. We hypothesized that primary cilia are required for maximal activation of the osmotic response of renal epithelial cells and that ciliary TRPM3 and TRPV4 mediate that response. Ciliated [murine epithelial cells from the renal inner medullary collecting duct (mIMCD-3) and 176-...
Source: AJP: Renal Physiology - April 7, 2017 Category: Urology & Nephrology Authors: Siroky, B. J., Kleene, N. K., Kleene, S. J., Varnell, C. D., Comer, R. G., Liu, J., Lu, L., Pachciarz, N. W., Bissler, J. J., Dixon, B. P. Tags: RESEARCH ARTICLE Source Type: research
Zebrafish mesonephric renin cells are functionally conserved and comprise two distinct morphological populations
Zebrafish provide an excellent model in which to assess the role of the renin-angiotensin system in renal development, injury, and repair. In contrast to mammals, zebrafish kidney organogenesis terminates with the mesonephros. Despite this, the basic functional structure of the nephron is conserved across vertebrates. The relevance of teleosts for studies relating to the regulation of the renin-angiotensin system was established by assessing the phenotype and functional regulation of renin-expressing cells in zebrafish. Transgenic fluorescent reporters for renin (ren), smooth muscle actin (acta2), and platelet-derived grow...
Source: AJP: Renal Physiology - April 7, 2017 Category: Urology & Nephrology Authors: Rider, S. A., Christian, H. C., Mullins, L. J., Howarth, A. R., MacRae, C. A., Mullins, J. J. Tags: RESEARCH ARTICLE Source Type: research
(5R)-5-hydroxytriptolide ameliorates lupus nephritis in MRL/lpr mice by preventing infiltration of immune cells
In this study, we aimed to investigate the therapeutic effects of LLDT-8 on lupus nephritis in MRL/lpr mice, a model of systemic lupus erythematosus. Compared with the vehicle group, different clinical parameters were improved upon LLDT-8 treatment as follows: prolonged life span of mice, decreased proteinuria, downregulated blood urea nitrogen and serum creatinine, reduced glomerular IgG deposits, and ameliorated histopathology. A decreased expression of the inflammatory cytokines IFN-, IL-17, IL-6, and TNF-α was also observed in the kidney of LLDT-8 treated MRL/lpr mice. Moreover, infiltration of T cells in the kid...
Source: AJP: Renal Physiology - April 7, 2017 Category: Urology & Nephrology Authors: Zhang, L.-y., Li, H., Wu, Y.-w., Cheng, L., Yan, Y.-x., Yang, X.-q., Zhu, F.-h., He, S.-j., Tang, W., Zuo, J.-p. Tags: RESEARCH ARTICLE Source Type: research
MDM2 mediates fibroblast activation and renal tubulointerstitial fibrosis via a p53-independent pathway
It is well recognized that murine double minute gene 2 (MDM2) plays a critical role in cell proliferation and inflammatory processes during tumorigenesis. It is also reported that MDM2 is expressed in glomeruli and involved in podocyte injury. However, whether MDM2 is implicated in renal fibrosis remains unclear. Here we investigated the role of MDM2 in tubulointerstitial fibrosis (TIF). By immunohistochemical staining and Western blotting we confirmed that MDM2 is upregulated in the tubulointerstitial compartment in patients with TIF and unilateral urethral obstruction (UUO) mice, which mainly originates from myofibroblas...
Source: AJP: Renal Physiology - April 7, 2017 Category: Urology & Nephrology Authors: Ye, C., Tang, H., Zhao, Z., Lei, C.-T., You, C.-Q., Zhang, J., Gao, P., He, F.-F., Chen, S., Wang, Y.-M., Zhang, C., Su, H. Tags: RESEARCH ARTICLE Source Type: research
Inhibition of T-cell activation by the CTLA4-Fc Abatacept is sufficient to ameliorate proteinuric kidney disease
In this study we used the soluble CTLA4-Fc fusion protein Abatacept to block cell surface B7-1, preventing the cellular interaction and inhibiting T-cell activation. When Abatacept was dosed in an animal model of diabetes-induced albuminuria, it reduced albuminuria in both prevention and intervention modes. The number of T-cells infiltrating the kidneys of DN animals correlated with the degree of albuminuria, and treatment with Abatacept reduced the number of renal T-cells. As B7-1 induction has been recently proposed to underlie podocyte damage in DN, Abatacept could be efficacious in DN by protecting podocytes. However, ...
Source: AJP: Renal Physiology - April 7, 2017 Category: Urology & Nephrology Authors: Herrera, M., Söderberg, M., Sabirsh, A., Valastro, B., Mölne, J., Santamaria, B., Valverde, A. M., Guionaud, S., Heasman, S., Bigley, A., Jermutus, L., Rondinone, C., Coghlan, M., Baker, D., Quinn, C. M. Tags: RESEARCH ARTICLE Source Type: research
Aquaporin-2 membrane targeting: still a conundrum
The targeting of the water channel aquaporin-2 (AQP2) to the apical plasma membrane of kidney collecting duct principal cells is regulated mainly by the antidiuretic peptide hormone arginine vasopressin (AVP). This process is of crucial importance for the maintenance of body water homeostasis. In this brief review we assess the role of cyclic adenosine monophosphate (cAMP) and discuss the emerging concept that type 2 AVP receptor (V2R)-mediated AQP2 trafficking is cAMP-independent. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - April 7, 2017 Category: Urology & Nephrology Authors: Olesen, E. T. B., Fenton, R. A. Tags: REVIEW Source Type: research
Sleeping beauty: awakening urothelium from its slumber
The bladder urothelium is essentially quiescent but regenerates readily upon injury. The process of urothelial regeneration harkens back to the process of urothelial development whereby urothelial stem/progenitor cells must proliferate and terminally differentiate to establish all three urothelial layers. How the urothelium regulates the level of proliferation and the timing of differentiation to ensure the precise degree of regeneration is of significant interest in the field. Without a carefully-orchestrated process, urothelial regeneration may be inadequate, thereby exposing the host to toxins or pathogens. Alternativel...
Source: AJP: Renal Physiology - April 7, 2017 Category: Urology & Nephrology Authors: Balsara, Z. R., Li, X. Tags: REVIEW Source Type: research
Immunity and inflammation in diabetic kidney disease: translating mechanisms to biomarkers and treatment targets
This article reviews the involvement of the immune system in DKD and identifies important roles of key immune and inflammatory mediators. One of the most recently identified biomarkers is serum amyloid A, which appears to be relatively specific for DKD. Novel and evolving treatment approaches target protein kinases, transcription factors, chemokines, adhesion molecules, growth factors, advanced glycation end-products, and other inflammatory molecules. This is the beginning of a new era in the understanding and treatment of DKD, and we may have finally reached a tipping point in our fight against the growing burden of DKD. ...
Source: AJP: Renal Physiology - April 7, 2017 Category: Urology & Nephrology Authors: Pichler, R., Afkarian, M., Dieter, B. P., Tuttle, K. R. Tags: REVIEW Source Type: research
USP40 gene knockdown disrupts glomerular permeability in zebrafish
Unbiased transcriptome profiling and functional genomics approaches have identified ubiquitin-specific protease 40 (USP40) as a highly specific glomerular transcript. This gene product remains uncharacterized, and its biological function is completely unknown. Here, we showed that mouse and rat glomeruli exhibit specific expression of the USP40 protein, which migrated at 150 kDa and was exclusively localized in the podocyte cytoplasm of the adult kidney. Double-labeling immunofluorescence staining and confocal microscopy analysis of fetal and neonate kidney samples revealed that USP40 was also expressed in the vasculature,...
Source: AJP: Renal Physiology - April 1, 2017 Category: Urology & Nephrology Authors: Takagi, H., Nishibori, Y., Katayama, K., Katada, T., Takahashi, S., Kiuchi, Z., Takahashi, S.-I., Kamei, H., Kawakami, H., Akimoto, Y., Kudo, A., Asanuma, K., Takematsu, H., Yan, K. Tags: RESEARCH ARTICLE Source Type: research
Chronic kidney disease promotes chronic inflammation in visceral white adipose tissue
White adipose tissue plays an important role in the development of metabolic disturbance, which is a common feature in patients with chronic kidney disease (CKD). The effect of CKD on white adipose tissue remains poorly appreciated. Here, we evaluated the inflammatory potential of visceral white adipose tissue in a rat model of CKD. The results showed that production of proinflammatory cytokines and infiltration of macrophage in the tissue were increased significantly in CKD rats compared with sham rats. Moreover, the primary adipocytes and stromal vascular fraction under the condition of CKD could trigger the inflammatory...
Source: AJP: Renal Physiology - April 1, 2017 Category: Urology & Nephrology Authors: Xiang, D. M., Song, X. Z., Zhou, Z. M., Liu, Y., Dai, X. Y., Huang, X. L., Hou, F. F., Zhou, Q. G. Tags: RESEARCH ARTICLE Source Type: research
ENaC and ROMK activity are inhibited in the DCT2/CNT of TgWnk4PHAII mice
Mice transgenic for genomic segments harboring PHAII (pseudohypoaldosteronism type II) mutant Wnk4 (with-No-Lysine kinase 4) (TgWnk4PHAII) have hyperkalemia which is currently believed to be the result of high activity of Na-Cl cotransporter (NCC). This leads to decreasing Na+ delivery to the distal nephron segment including late distal convoluted tubule (DCT) and connecting tubule (CNT). Since epithelial Na+ channel (ENaC) and renal outer medullary K+ channel (ROMK or Kir4.1) are expressed in the late DCT and play an important role in mediating K+ secretion, the aim of the present study is to test whether ROMK and ENaC ac...
Source: AJP: Renal Physiology - April 1, 2017 Category: Urology & Nephrology Authors: Zhang, C., Wang, L., Su, X.-T., Zhang, J., Lin, D.-H., Wang, W.-H. Tags: RESEARCH ARTICLE Source Type: research
Markers of endothelial damage in patients with chronic kidney disease on hemodialysis
Patients with Stage 5 chronic kidney disease who are on hemodialysis (HD) remain in a chronic inflammatory state, characterized by the accumulation of uremic toxins that induce endothelial damage and cardiovascular disease (CVD). Our aim was to examine microvesicles (MVs), monocyte subpopulations, and angiopoietins (Ang) to identify prognostic markers in HD patients with or without diabetes mellitus (DM). A total of 160 prevalent HD patients from 10 centers across Spain were obtained from the Biobank of the Nephrology Renal Network (Madrid, Spain): 80 patients with DM and 80 patients without DM who were matched for clinica...
Source: AJP: Renal Physiology - April 1, 2017 Category: Urology & Nephrology Authors: Carmona, A., Agüera, M. L., Luna-Ruiz, C., Buendia, P., Calleros, L., Garcia-Jerez, A., Rodriguez-Puyol, M., Arias, M., Arias-Guillen, M., de Arriba, G., Ballarin, J., Bernis, C., Fernandez, E., Garcia-Rebollo, S., Mancha, J., del Peso, G., Perez, Tags: RESEARCH ARTICLE Source Type: research
A new microscope for the kidney: mathematics
(Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - April 1, 2017 Category: Urology & Nephrology Authors: Layton, A. T. Tags: EDITORIAL FOCUS Source Type: research
Diabetes, hypertension, and chronic kidney disease progression: role of DPP4
The protein dipeptidyl peptidase 4 (DPP4) is a target in diabetes management and reduction of associated cardiovascular risk. Inhibition of the enzymatic function and genetic deletion of DPP4 is associated with tremendous benefits to the heart, vasculature, adipose tissue, and the kidney in rodent models of obesity, diabetes and hypertension, and associated complications. The recently concluded, "Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus—Thrombolysis in Myocardial Infarction 53" trial revealed a reduction in proteinuria in chronic kidney disease patients (stages 1-3). The...
Source: AJP: Renal Physiology - April 1, 2017 Category: Urology & Nephrology Authors: Nistala, R., Savin, V. Tags: PERSPECTIVE Source Type: research
Ventilator-induced lung injury increases expression of endothelial inflammatory mediators in the kidney
In critical illness, such as sepsis or the acute respiratory distress syndrome, acute kidney injury (AKI) is common and associated with increased morbidity and mortality. Mechanical ventilation in critical illnesses is also a risk factor for AKI, but it is potentially modifiable. Injurious ventilation strategies may lead to the systemic release of inflammatory mediators from the lung due to ventilator induced lung injury (VILI). The systemic consequences of VILI are difficult to differentiate clinically from other systemic inflammatory syndromes, such as sepsis. The purpose of this study was to identify unique changes in t...
Source: AJP: Renal Physiology - April 1, 2017 Category: Urology & Nephrology Authors: Hepokoski, M., Englert, J. A., Baron, R. M., Crotty-Alexander, L. E., Fuster, M. M., Beitler, J. R., Malhotra, A., Singh, P. Tags: RAPID REPORT Source Type: research
