Mechanism of aldosterone-induced increase of K+ conductance in early distal renal tubule cells of the frog

1989 ◽  
Vol 111 (3) ◽  
pp. 277-289 ◽  
Author(s):  
Wenhui Wang ◽  
Robert M. Henderson ◽  
John Geibel ◽  
Stanley White ◽  
Gerhard Giebisch
2004 ◽  
Vol 379 (1) ◽  
pp. 89-97 ◽  
Author(s):  
Yu-Lin YANG ◽  
Lea-Yea CHUANG ◽  
Jinn-Yuh GUH ◽  
Shu-Fen LIU ◽  
Min-Yuan HUNG ◽  
...  

Diabetic nephropathy is characterized by early hypertrophy in both glomerular and tubuloepithelial elements. However, no studies to date have established a direct causal link between hyperglycaemia and renal hypertrophy. Our previous studies have found that high glucose does not induce cellular hypertrophy or expression of TGF-β1 (transforming growth factor-β1) in distal renal tubule cells [Yang, Guh, Yang, Lai, Tsai, Hung, Chang and Chuang (1998) J. Am. Soc. Nephrol. 9, 182–193]. In the present study, we used AGEs (advanced glycation end-products) to mimic long-term hyperglycaemia. Similar to glucose, AGEs did not induce TGF-β1 mRNA in distal renal tubule cells [MDCK (Madin–Darby canine kidney) cells]; however, TGF-β1 bioactivity was increased significantly. This result indicated post-translational regulation. Since TSP-1 (thrombospondin-1) has been demonstrated to activate latent TGF-β1 in a variety of systems, the following experiments were performed. We found that AGEs dose-dependently increased both intracellular and extracellular levels of TSP-1. Purified TSP-1, like AGEs, increased the cellular protein content. Furthermore, anti-TSP-1 neutralizing antibodies attenuated the AGE-induced increase in TGF-β1 bioactivity and hypertrophy. Thus TSP-1 might mediate AGE-induced distal renal tubule hypertrophy. In addition, we observed several putative transcription factor binding sites in the TSP-1 promoter, including those for AP-1 (activator protein-1), CREB (cAMP response element binding protein), NF-κB (nuclear factor-κB), SRF (serum response factor) and HSF (heat-shock factor), by sequence mapping. We used an enhancer assay to screen possible transcription factors involved. We showed that AP-1 and CREB were specifically induced by AGEs; furthermore, TFD (transcription factor decoy) for AP-1 could attenuate the AGE-induced increases in TSP-1 levels and cellular hypertrophy. Thus regulation of TSP-1 might be critical for hyperglycaemic distal tubule hypertrophy. Furthermore, TSP-1 TFD might be a potential approach to ameliorate diabetic renal hypertrophy.


1998 ◽  
Vol 54 (4) ◽  
pp. 1139-1149 ◽  
Author(s):  
Ingeborg A. Hauser ◽  
Michael Koziolek ◽  
Ulrich Hopfer ◽  
Frank Thévenod

1989 ◽  
Vol 2 (7) ◽  
pp. 563-566 ◽  
Author(s):  
Maria-Luisa Melzi ◽  
Alejandro Bertorello ◽  
Yutaka Fukuda ◽  
Ingrid Muldin ◽  
Fabio Sereni ◽  
...  

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Bo Zhang ◽  
Kai Chen ◽  
Zhongjie Sun

A disintegrin and metalloproteinase 17 (ADAM17) is a ubiquitously expressed membrane-bound sheddase that cleaves a diverse variety of membrane-bound molecules, including cytokines, growth factors, and their receptors to activate or inactivate various cellular signaling pathways. Although it was reported that ADAM17 may mediate renal diseases, the role of ADAM17 in the regulation of normal kidney function has never been identified. The objective of this study is to investigate whether renal ADAM17 plays a role in maintaining normal kidney function and structure. Tamoxifen-inducible kidney-specific cre (Ksp) and ADAM17-floxed mice were cross-bred for generating Ksp/ADAM17-floxed mice. Injection of tamoxifen initiated deletion of the ADAM17 gene in renal tubule cells. We found that conditional kidney-specific knockout of ADAM1 7 gene (Ksp-ADAM17 -/-) decreased urinary creatinine and sodium excretion were decreased in Ksp-ADAM17 -/- mice, indicating that ADAM17 gene deficiency impairs kidney function. H&E staining showed glomerulus collapse and tubule dilation in Ksp-ADAM17 -/- mice. The epithelial cells fall off into the lumen in the renal tubule. Mesangial expansion and fibrosis were found in glomeruli in Ksp-ADAM17 -/- mice. Moreover, apoptosis was increased in tubule cells in both cortex and medulla areas in Ksp-ADAM17 -/- mice. In conclusion, ADAM17 is critical to the maintenance of normal renal function and structure.


1992 ◽  
Vol 263 (5) ◽  
pp. R1086-R1092 ◽  
Author(s):  
D. A. Terreros ◽  
H. Kanli

Osmoregulatory Ca2+ signaling in hypotonic solutions was studied with videometric techniques in 158 proximal renal tubules isolated from the teleost Carassius auratus. Absence of extracellular Ca2+, hypoxia (23 mmHg), or NaCN (3 mM) did not alter regulatory volume decreases (RVD). Nevertheless, decrements of intracellular Ca2+ via the A23187 ionophore or after intracellular Ca2+ chelation with indo-1/AM (5 microM) inhibited RVD. In tubules depleted of Ca2+, RVD could only be fully elicited when intracellular Ca2+ pulses were given within 1 min after hypotonic stimulation. While inhibition of Ca2+ release from the endoplasmic reticulum (ER) with 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8, 50 microM) blunted RVD, some of its effects could be reversed with the anion carrier tributyltin (1 microM). Dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP, 0.5 and 1.0 mM) and forskolin (0.25 mM) also impeded RVD; however, their effects could be partially reversed with the K+ ionophore gramicidin (0.5 microM). In conclusion, in Carassius auratus proximal renal tubule cells, RVD is activated by an intracellular Ca2+ signal that likely emanates from the ER and not from the extracellular media or the mitochondrial Ca2+ pool. Ca2+ activation of a cAMP-modulated osmoregulatory K+ channel appears to play an important role.


1999 ◽  
Vol 35 (6) ◽  
pp. 314-317 ◽  
Author(s):  
James Springate ◽  
Kenneth Chan ◽  
Hong Lu ◽  
Sherry Davies ◽  
Mary Taub
Keyword(s):  

1986 ◽  
Vol 64 (10) ◽  
pp. 2213-2217 ◽  
Author(s):  
Sherwin S. Desser ◽  
Jǐrí Lom ◽  
Iva Dyková

Pseudoplasmodia and mature spores of Sphaerospora ohlmacheri (Whinery, 1893) n.comb. were found in the renal tubules and in the space of the Bowman's capsule of 2nd-year tadpoles of the bullfrog, Rana catesbeiana. Fresh spores and the sporogenic stages of S. ohlmacheri from tissue imprints and histological sections are described and illustrated. Dystrophic changes of renal tubule cells characterized by degeneration associated with hyaline droplets often accompanied the presence of the parasite. Features of the genera Leptotheca, Wardia, and Sphaerospora are discussed.


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