Deletion of {beta}1-integrin in collecting duct principal cells leads to tubular injury and renal medullary fibrosis
The renal collecting duct (CD) contains two major cell types, intercalated (ICs) and principal cells (PCs). A previous report showed that deletion of β1-integrin in the entire renal CD causes defective CD morphogenesis resulting in kidney dysfunction. However, subsequent deletion of β1-integrin specifically in ICs and PCs, respectively, did not cause any morphological defects in the CDs. The discrepancy between these studies prompts us to reinvestigate the role of β1-integrin in CD cells, specifically in the PCs. We conditionally deleted β1-integrin in mouse CD PCs using a specific aquaporin-2 (AQP2) pr...
Source: AJP: Renal Physiology - October 9, 2017 Category: Urology & Nephrology Authors: Mamuya, F. A., Xie, D., Lei, L., Huang, M., Tsuji, K., Capen, D. E., Yang, B., Weissleder, R., Paunescu, T. G., Lu, H. A. J. Tags: RESEARCH ARTICLE Source Type: research
Dopamine reduces cell surface Na+/H+ exchanger-3 protein by decreasing NHE3 exocytosis and cell membrane recycling
In conclusion, among the many mechanisms by which DA reduces apical membrane NHE3 and induces proximal tubule natriuresis, one additional mechanism is inhibition of exocytotic insertion and reinsertion of NHE3 in the apical cell surface. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - October 9, 2017 Category: Urology & Nephrology Authors: Hu, M. C., Bobulescu, I. A., Quinones, H., Gisler, S. M., Moe, O. W. Tags: RESEARCH ARTICLE Source Type: research
Sex and gender differences in hypertensive kidney injury
Hypertension is a complex, multifaceted disorder, affecting ~1 in 3 adults in the United States. Although hypertension occurs in both men and women, there are distinct sex differences in the way in which they develop hypertension, with women having a lower incidence of hypertension until the sixth decade of life. Despite observed sex differences in hypertension, little is known about the molecular mechanisms underlying the development of hypertension in females, primarily because of their underrepresentation in both clinical and experimental animal studies. The first goal of this review is to provide a concise overview of ...
Source: AJP: Renal Physiology - October 9, 2017 Category: Urology & Nephrology Authors: Sullivan, J. C., Gillis, E. E. Tags: REVIEW Source Type: research
Tumor necrosis factor-{alpha}, kidney function, and hypertension
Hypertension is considered to be a low-grade inflammatory condition characterized by the presence of various proinflammatory cytokines. Tumor necrosis factor-α (TNF-α) is a constituent of the proinflammatory cytokines that is associated with salt-sensitive hypertension (SSH) and related renal injury. Elevated angiotensin II (ANG II) and other factors such as oxidative stress conditions promote TNF-α formation. Many recent studies have provided evidence that TNF-α exerts a direct renal action by regulating hemodynamic and excretory function in the kidney. The cytokine incites a strong natriuretic res...
Source: AJP: Renal Physiology - October 9, 2017 Category: Urology & Nephrology Authors: Mehaffey, E., Majid, D. S. A. Tags: REVIEW Source Type: research
An inhibitor of histone deacetylase 6 activity, ACY-1215, reduces cAMP and cyst growth in polycystic kidney disease
Adult-onset autosomal-dominant polycystic kidney disease (ADPKD) is caused by mutations in either the PKD1 or PKD2 gene, leading to malfunction of their gene products, polycystin 1 or 2. Histone deacetylase 6 (HDAC6) expression and activity are increased in PKD1 mutant renal epithelial cells. Here we studied the effect of ACY-1215, a specific HDAC6 inhibitor, on cyst growth in ADPKD. Treatment with ACY-1215 slowed cyst growth in a mouse model of ADPKD that forms massive cysts within 3 wk after knockout of polycystin 1 function. It also prevented cyst formation in MDCK.2 cells, an in vitro model of cystogenesis, and in an A...
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Yanda, M. K., Liu, Q., Cebotaru, L. Tags: RESEARCH ARTICLE Source Type: research
Early, but not late, treatment with human umbilical cord blood-derived mesenchymal stem cells attenuates cisplatin nephrotoxicity through immunomodulation
In this study, human umbilical cord blood (hUCB)-derived MSCs were used to compare the effects and mechanisms of early and late MSC therapy in a murine model. After cisplatin injection into C57BL/6 mice, hUCB-MSCs were administered on day 1 (early treatment) or day 3 (late treatment). With early treatment, cisplatin nephrotoxicity was attenuated as evidenced by decreased blood urea nitrogen (BUN) and reduced apoptosis and tubular injury scores on day 3. Early treatment resulted in downregulation of intrarenal monocyte chemotactic protein-1 and IL-6 expression and upregulation of IL-10 and VEGF expression. Flow cytometric a...
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Park, J. H., Jang, H. R., Kim, D. H., Kwon, G. Y., Lee, J. E., Huh, W., Choi, S. J., Oh, W., Oh, H. Y., Kim, Y.-G. Tags: RESEARCH ARTICLE Source Type: research
Regulation of PDZ domain-containing 1 (PDZK1) expression by hepatocyte nuclear factor-1{alpha} (HNF1{alpha}) in human kidney
In the renal proximal tubule the secretion and reabsorption of glomerularly filtrated compounds is realized by a functional network of uptake and efflux transporters. The activity and localization of several transporters expressed at the apical tubular membrane are regulated by the membrane-associated protein PDZ domain-containing 1 (PDZK1). We aimed to characterize the transcriptional regulation of this modulator of renal transport. Coexpression analyses of PDZK1 and putative regulators were performed using human kidney samples. Protein and mRNA expression of PDZK1 in renal proximal tubule epithelial cells after adenovira...
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Prestin, K., Hussner, J., Ferreira, C., Seibert, I., Breitung, V., Zimmermann, U., Meyer zu Schwabedissen, H. E. Tags: RESEARCH ARTICLE Source Type: research
Ketamine-induced bladder fibrosis involves epithelial-to-mesenchymal transition mediated by transforming growth factor-{beta}1
Bladder wall fibrosis is a major complication of ketamine-induced cystitis (KC), but the underlying pathogenesis is poorly understood. The aim of the present study was to elucidate the mechanism of ketamine-induced fibrosis in association with epithelial-to-mesenchymal transition (EMT) mediated by transforming growth factor-β1 (TGF-β1). Sprague-Dawley rats were randomly distributed into four groups, which received saline, ketamine, ketamine combined with a TGF-β receptor inhibitor (SB-505124) for 16 wk, or 12 wk of ketamine and 4 wk of abstinence. In addition, the profibrotic effect of ketamine was confirmed...
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Wang, J., Chen, Y., Gu, D., Zhang, G., Chen, J., Zhao, J., Wu, P. Tags: RESEARCH ARTICLE Source Type: research
Heavy metal suicide
(Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Linkermann, A., Stockwell, B., Vanden Berghe, T. Tags: EDITORIAL FOCUS Source Type: research
Sodium intake affects sex difference in aldosterone concentration
(Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Kitada, K., Nishiyama, A. Tags: EDITORIAL FOCUS Source Type: research
Protection of kidneys by magnesium in cisplatin chemotherapy: a fight between two metals
(Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Li, F., Livingston, M. J., Dong, Z. Tags: EDITORIAL FOCUS Source Type: research
Harnessing basic and clinic tools to evaluate SGLT2 inhibitor nephrotoxicity
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a new class of medications that target the transporter that reabsorbs ~90% of glucose in the S1 segment of the proximal convoluted tubule. As a result, SGLT2 inhibition increases urinary glucose excretion, effectively lowering plasma glucose levels. In addition to reducing hemoglobin A1c levels, these drugs also lower body weight, blood pressure, and uric acid levels in Type 2 diabetes mellitus (T2DM) patients. Importantly, empagliflozin has been observed to slow progression of kidney disease and reduce dialysis requirements in T2DM patients. However, the Food and Drug ...
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Saly, D. L., Perazella, M. A. Tags: PERSPECTIVE Source Type: research
Inflammation and premature aging in advanced chronic kidney disease
Systemic inflammation in end-stage renal disease is an established risk factor for mortality and a catalyst for other complications, which are related to a premature aging phenotype, including muscle wasting, vascular calcification, and other forms of premature vascular disease, depression, osteoporosis, and frailty. Uremic inflammation is also mechanistically related to mechanisms involved in the aging process, such as telomere shortening, mitochondrial dysfunction, and altered nutrient sensing, which can have a direct effect on cellular and tissue function. In addition to uremia-specific causes, such as abnormalities in ...
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Kooman, J. P., Dekker, M. J., Usvyat, L. A., Kotanko, P., van der Sande, F. M., Schalkwijk, C. G., Shiels, P. G., Stenvinkel, P. Tags: REVIEW Source Type: research
UCP2 attenuates apoptosis of tubular epithelial cells in renal ischemia-reperfusion injury
Uncoupling protein-2 (UCP2) plays critical roles in energy metabolism and cell survival. Previous investigations showed that UCP2 regulated the production of extracellular matrix and renal fibrosis. However, little is known about UCP2 in acute kidney injury (AKI). Here, we used Ucp2 knockout mice to investigate the role of UCP2 in an AKI model generated by renal ischemia-reperfusion (I/R) injury. The Ucp2 global knockout mice were born and grew normally without kidney histological abnormality or renal dysfunction. Compared with littermates, deletion of Ucp2 exacerbated I/R-induced AKI whereas increase of UCP2 by conjugated...
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Zhou, Y., Cai, T., Xu, J., Jiang, L., Wu, J., Sun, Q., Zen, K., Yang, J. Tags: RESEARCH ARTICLE Source Type: research
Aliskiren increases aquaporin-2 expression and attenuates lithium-induced nephrogenic diabetes insipidus
In conclusion, the direct renin inhibitor aliskiren upregulates AQP2 protein expression in inner medullary collecting duct principal cells and prevents lithium-induced nephrogenic diabetes insipidus likely via cAMP-PKA pathways. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Lin, Y., Zhang, T., Feng, P., Qiu, M., Liu, Q., Li, S., Zheng, P., Kong, Y., Levi, M., Li, C., Wang, W. Tags: RESEARCH ARTICLE Source Type: research
