The role of capsaicin-sensitive C-fiber afferent pathways in the control of micturition in spinal-intact and spinal cord-injured mice
We examined bladder and urethral sphincter activity in mice with or without spinal cord injury (SCI) after C-fiber afferent desensitization induced by capsaicin pretreatment and changes in electrophysiological properties of mouse bladder afferent neurons 4 wk after SCI. Female C57BL/6N mice were divided into four groups: 1) spinal intact (SI)-control, 2) SI-capsaicin pretreatment (Cap), 3) SCI-control, and 4) SCI-Cap groups. Continuous cystometry and external urethral sphincter (EUS)-electromyogram (EMG) were conducted under an awake condition. In the Cap groups, capsaicin (25, 50, or 100 mg/kg) was injected subcutaneously...
Source: AJP: Renal Physiology - September 11, 2017 Category: Urology & Nephrology Authors: Kadekawa, K., Majima, T., Shimizu, T., Wada, N., de Groat, W. C., Kanai, A. J., Goto, M., Yoshiyama, M., Sugaya, K., Yoshimura, N. Tags: RESEARCH ARTICLE Source Type: research
Inhibition of HDAC enhances STAT acetylation, blocks NF-{kappa}B, and suppresses the renal inflammation and fibrosis in Npr1 haplotype male mice
The objective of the present study was to determine the physiological efficacy and impact of all-trans-retinoic acid (ATRA) and sodium butyrate (NaBu) in ameliorating the renal fibrosis, inflammation, and hypertension in Npr1 gene-disrupted haplotype (1-copy; +/–) mice (50% expression levels of NPRA). Both ATRA and NaBu, either alone or in combination, decreased the elevated levels of renal proinflammatory and profibrotic cytokines and lowered blood pressure in Npr1+/– mice compared with untreated controls. The treatment with ATRA-NaBu facilitated the dissociation of histone deacetylase (HDAC) 1 and 2 from sign...
Source: AJP: Renal Physiology - September 11, 2017 Category: Urology & Nephrology Authors: Kumar, P., Gogulamudi, V. R., Periasamy, R., Raghavaraju, G., Subramanian, U., Pandey, K. N. Tags: RESEARCH ARTICLE Source Type: research
MIF-2/D-DT enhances proximal tubular cell regeneration through SLPI- and ATF4-dependent mechanisms
Macrophage migration inhibitory factor (MIF) is a cytokine with pleiotropic actions that is produced by several organs and cell types. Depending on the target cell and the inflammatory context, MIF can engage its two component receptor complex CD74 and CD44 and the chemokine receptors CXCR2/4. MIF is constitutively expressed in renal proximal tubular cells, stored in intracellular preformed pools, and released at a low rate. Recently, a second MIF-like protein (i.e., MIF-2/D-DT) has been characterized in mammals. Our study was aimed at examining the role of MIF-2/D-DT, which mediates tissue protection in the heart, in tubu...
Source: AJP: Renal Physiology - September 11, 2017 Category: Urology & Nephrology Authors: Ochi, A., Chen, D., Schulte, W., Leng, L., Moeckel, N., Piecychna, M., Averdunk, L., Stoppe, C., Bucala, R., Moeckel, G. Tags: RESEARCH ARTICLE Source Type: research
Long-term aldosterone administration increases renal Na+-Cl- cotransporter abundance in late distal convoluted tubule
Renal Na+-Cl– cotransporter (NCC) is expressed in early distal convoluted tubule (DCT) 1 and late DCT (DCT2). NCC activity can be stimulated by aldosterone administration, and the mechanism is assumed to depend on the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which inactivates glucocorticoids that would otherwise occupy aldosterone receptors. Because 11β-HSD2 in rat may only be abundantly expressed in DCT2 cells and not in DCT1 cells, it has been speculated that aldosterone specifically stimulates NCC activity in DCT2 cells. In mice, however, it is debated if 11β-HSD2 is expressed...
Source: AJP: Renal Physiology - September 11, 2017 Category: Urology & Nephrology Authors: Poulsen, S. B., Christensen, B. M. Tags: RESEARCH ARTICLE Source Type: research
Unique sex- and age-dependent effects in protective pathways in acute kidney injury
Sex and age influence susceptibility to acute kidney injury (AKI), with young females exhibiting lowest incidence. In these studies, we investigated mechanisms which may underlie the sex/age-based dissimilarities. Cisplatin (Cp)-induced AKI resulted in morphological evidence of injury in all groups. A minimal rise in plasma creatinine (PCr) was seen in Young Females, whereas in Aged Females, PCr rose precipitously. Relative to Young Males, Aged Males showed significantly, but temporally, comparably elevated PCr. Notably, Aged Females showed significantly greater mortality, whereas Young Females exhibited none. Tissue KIM-1...
Source: AJP: Renal Physiology - September 11, 2017 Category: Urology & Nephrology Authors: Boddu, R., Fan, C., Rangarajan, S., Sunil, B., Bolisetty, S., Curtis, L. M. Tags: RESEARCH ARTICLE Source Type: research
Store-operated calcium entry suppressed the TGF-{beta}1/Smad3 signaling pathway in glomerular mesangial cells
Our previous study demonstrated that the abundance of extracellular matrix proteins was suppressed by store-operated Ca2+ entry (SOCE) in mesangial cells (MCs). The present study was conducted to investigate the underlying mechanism focused on the transforming growth factor-β1 (TGF-β1)/Smad3 pathway, a critical pathway for ECM expansion in diabetic kidneys. We hypothesized that SOCE suppressed ECM protein expression by inhibiting this pathway in MCs. In cultured human MCs, we observed that TGF-β1 (5 ng/ml for 15 h) significantly increased Smad3 phosphorylation, as evaluated by immunoblot. However, this respo...
Source: AJP: Renal Physiology - September 11, 2017 Category: Urology & Nephrology Authors: Chaudhari, S., Li, W., Wang, Y., Jiang, H., Ma, Y., Davis, M. E., Zuckerman, J. E., Ma, R. Tags: RESEARCH ARTICLE Source Type: research
Src family kinases in chronic kidney disease
Src family kinases (SFKs) belong to nonreceptor protein tyrosine kinases and have been implicated in the regulation of numerous cellular processes, including cell proliferation, differentiation, migration and invasion, and angiogenesis. The role and mechanisms of SFKs in tumorgenesis have been extensively investigated, and some SFK inhibitors are currently under clinical trials for tumor treatment. Recent studies have also demonstrated the importance of SFKs in regulating the development of various fibrosis-related chronic diseases (e.g., idiopathic pulmonary fibrosis, liver fibrosis, renal fibrosis, and systemic sclerosis...
Source: AJP: Renal Physiology - September 11, 2017 Category: Urology & Nephrology Authors: Wang, J., Zhuang, S. Tags: REVIEW Source Type: research
Biophysics and biofluid dynamics of primary cilia: evidence for and against the flow-sensing function
Primary cilia have been called "the forgotten organelle" for over 20 yr. As cilia now have their own journal and several books devoted to their study, perhaps it is time to reconsider the moniker "forgotten organelle." In fact, during the drafting of this review, 12 relevant publications have been issued; we therefore apologize in advance for any relevant work we inadvertently omitted. What purpose is yet another ciliary review? The primary goal of this review is to specifically examine the evidence for and against the hypothesized flow-sensing function of primary cilia expressed by differentiated epithelia within a kidney...
Source: AJP: Renal Physiology - September 11, 2017 Category: Urology & Nephrology Authors: Nag, S., Resnick, A. Tags: REVIEW Source Type: research
Increased susceptibility to structural acute kidney injury in a mouse model of presymptomatic cardiomyopathy
The early events that signal renal dysfunction in presymptomatic heart failure are unclear. We tested the hypothesis that functional and mechanistic changes occur in the kidney that precede the development of symptomatic heart failure. We employed a transgenic mouse model with cardiomyocyte-specific overexpression of mutant α-B-crystallin that develops slowly progressive cardiomyopathy. Presymptomatic transgenic mice displayed an increase in serum creatinine (1.17 ± 0.34 vs. wild type 0.65 ± 0.16 mg/dl, P < 0.05) and in urinary neutrophil gelatinase-associated lipocalin (NGAL; 278.92 ± 176.24 ...
Source: AJP: Renal Physiology - September 1, 2017 Category: Urology & Nephrology Authors: Pleasant, L., Ma, Q., Devarajan, M., Parameswaran, P., Drake, K., Siroky, B., Shay-Winkler, K., Robbins, J., Devarajan, P. Tags: RESEARCH ARTICLE Source Type: research
Spatiotemporal analysis of spontaneous myogenic contractions in the urinary bladder of the rabbit: timing and patterns reflect reported electrophysiology
The dynamics of propagating myogenic contractions in the wall of the resting ex vivo urinary bladder of the rabbit were characterized by spatiotemporal maps and related to cyclic variation in intravesical pressure (Pves). Patches of propagating contractions (PPCs) enlarged and involuted in near synchrony with peaks in Pves [mean 3.85 ± 0.3 cycles per minute (cpm)] and were preceded by regions of stretch. The maximum area of the bladder undergoing contraction (55.28 ± 2.65%) and the sizes of individual PPCs (42.61 ± 1.65 mm2) coincided with the peak in Pves. PPCs originated and propagated within tempora...
Source: AJP: Renal Physiology - September 1, 2017 Category: Urology & Nephrology Authors: Hulls, C. M., Lentle, R. G., King, Q. M., Reynolds, G. W., Chambers, J. P. Tags: RESEARCH ARTICLE Source Type: research
The regulatory 1{alpha} subunit of protein kinase A modulates renal cystogenesis
The failure of the polycystins (PCs) to function in primary cilia is thought to be responsible for autosomal dominant polycystic kidney disease (ADPKD). Primary cilia integrate multiple cellular signaling pathways, including calcium, cAMP, Wnt, and Hedgehog, which control cell proliferation and differentiation. It has been proposed that mutated PCs result in reduced intracellular calcium, which in turn upregulates cAMP, protein kinase A (PKA) signaling, and subsequently other proliferative signaling pathways. However, the role of PKA in ADPKD has not been directly ascertained in vivo, although the expression of the main re...
Source: AJP: Renal Physiology - September 1, 2017 Category: Urology & Nephrology Authors: Ye, H., Wang, X., Constans, M. M., Sussman, C. R., Chebib, F. T., Irazabal, M. V., Young, W. F., Harris, P. C., Kirschner, L. S., Torres, V. E. Tags: RESEARCH ARTICLE Source Type: research
Lithium-induced NDI: acetazolamide reduces polyuria but does not improve urine concentrating ability
Lithium is the mainstay treatment for patients with bipolar disorder, but it generally causes nephrogenic diabetes insipidus (NDI), a disorder in which the renal urine concentrating ability has become vasopressin insensitive. Li-NDI is caused by lithium uptake by collecting duct principal cells and downregulation of aquaporin-2 (AQP2) water channels, which are essential for water uptake from tubular urine. Recently, we found that the prophylactic administration of acetazolamide to mice effectively attenuated Li-NDI. To evaluate whether acetazolamide might benefit lithium-treated patients, we administered acetazolamide to m...
Source: AJP: Renal Physiology - September 1, 2017 Category: Urology & Nephrology Authors: de Groot, T., Doornebal, J., Christensen, B. M., Cockx, S., Sinke, A. P., Baumgarten, R., Bedford, J. J., Walker, R. J., Wetzels, J. F. M., Deen, P. M. T. Tags: RESEARCH ARTICLE Source Type: research
Interplay between renal endothelin and purinergic signaling systems
Alterations in extracellular fluid volume regulation and sodium balance may result in the development and maintenance of salt-dependent hypertension, a major risk factor for cardiovascular disease. Numerous pathways contribute to the regulation of sodium excretion and blood pressure, including endothelin and purinergic signaling. Increasing evidence suggests a link between purinergic receptor activation and endothelin production within the renal collecting duct as a means of promoting natriuresis. A better understanding of the relationship between these two systems, especially in regard to sodium homeostasis, will fill a s...
Source: AJP: Renal Physiology - September 1, 2017 Category: Urology & Nephrology Authors: Gohar, E. Y., Kasztan, M., Pollock, D. M. Tags: REVIEW Source Type: research
Stimulation of the pelvic nerve increases bladder capacity in the prostaglandin E2 rat model of overactive bladder
Overactive bladder (OAB) syndrome is a highly prevalent condition that may lead to medical complications and decreased quality of life. Emerging therapies focusing on selective electrical stimulation of peripheral nerves associated with lower urinary tract function may provide improved efficacy and reduced side effects compared with sacral neuromodulation for the treatment of OAB symptoms. Prior studies investigating the effects of pelvic nerve (PelN) stimulation on lower urinary tract function were focused on promoting bladder contractions, and it is unclear whether selective stimulation of the PelN would be beneficial fo...
Source: AJP: Renal Physiology - September 1, 2017 Category: Urology & Nephrology Authors: Langdale, C. L., Hokanson, J. A., Sridhar, A., Grill, W. M. Tags: RESEARCH ARTICLE Source Type: research
(Pro)Renin receptor regulates potassium homeostasis through a local mechanism
(Pro)renin receptor (PRR) is highly expressed in the distal nephron, but it has an unclear functional implication. The present study was conducted to explore a potential role of renal PRR during high K+ (HK) loading. In normal Sprague-Dawley rats, a 1-wk HK intake increased renal expression of full-length PRR and urinary excretion of soluble PRR (sPRR). Administration of PRO20, a decoy peptide antagonist of PRR, in K+-loaded animals elevated plasma K+ level and decreased urinary K+ excretion, accompanied with suppressed urinary aldosterone excretion and intrarenal aldosterone levels. HK downregulated Na+-Cl– cotransp...
Source: AJP: Renal Physiology - September 1, 2017 Category: Urology & Nephrology Authors: Xu, C., Lu, A., Wang, H., Fang, H., Zhou, L., Sun, P., Yang, T. Tags: RESEARCH ARTICLE Source Type: research
