Minding the Gap

Facemire, Carie; Gurley, Susan B.

doi:10.1681/asn.2011040395

Cited by 3 publications

(3 citation statements)

References 18 publications

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“…Yet, mice with renin cell-specific deletion of Cx40 maintain the ability to recruit additional renin producing cells in response to salt depletion and ACE inhibition, whereas this response is eliminated in mice with global deletion of C×40. These observations suggest that gap junction coupling is not required for recruitment of additional renin cells during homeostatic challenges, but it appears to be necessary for proper localization of these cells both under basal conditions and during prolonged renin stimulation (83). …”

Section: Local Control Of Renin Releasementioning

confidence: 99%

Classical Renin‐Angiotensin System in Kidney Physiology

Sparks

Crowley

Gurley

et al. 2014

Comprehensive Physiology

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477

429

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The renin-angiotensin system has powerful effects in control of the blood pressure and sodium homeostasis. These actions are coordinated through integrated actions in the kidney, cardio-vascular system and the central nervous system. Along with its impact on blood pressure, the renin-angiotensin system also influences a range of processes from inflammation and immune responses to longevity. Here, we review the actions of the “classical” renin-angiotensin system, whereby the substrate protein angiotensinogen is processed in a two-step reaction by renin and angiotensin converting enzyme, resulting in the sequential generation of angiotensin I and angiotensin II, the major biologically active renin-angiotensin system peptide, which exerts its actions via type 1 and type 2 angiotensin receptors. In recent years, several new enzymes, peptides, and receptors related to the renin-angiotensin system have been identified, manifesting a complexity that was previously unappreciated. While the functions of these alternative pathways will be reviewed elsewhere in this journal, our focus here is on the physiological role of components of the “classical” renin-angiotensin system, with an emphasis on new developments and modern concepts.

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Section: Local Control Of Renin Releasementioning

confidence: 99%

Classical Renin‐Angiotensin System in Kidney Physiology

Sparks

Crowley

Gurley

et al. 2014

Comprehensive Physiology

Self Cite

477

429

View full text Add to dashboard Cite

show abstract

“…To date our knowledge of a role for gap junctions in the kidney and in diabetic nephropathy is limited. Glucose decreases GJ-conductance and disrupts cellular homeostasis in a variety of cell systems [19,20] and glucose-dependent down-regulation of Cx43 expression and GJ-communication has been reported in bovine retinal pericytes [21], endothelial [22], and epithelial cells [23]. Whilst the presence of GJs in the kidney has long been known, specific details regarding their function in the proximal tubule is sparse.…”

Section: Introductionmentioning

confidence: 99%

Visfatin Reduces Gap Junction Mediated Cell-to-Cell Communication in Proximal Tubule-Derived Epithelial Cells

Hills

Kerr

Wall

et al. 2013

Cell Physiol Biochem

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Background/Aims: In the current study we examined if the adipocytokine, visfatin, alters connexin-mediated intercellular communication in proximal tubule-derived epithelial cells. Methods: The effects of visfatin (10-200ng/mL) on cell viability and cytotoxicity in HK2-cells were assessed by MTT, crystal violet and lactate dehydrogenase assays. Western blot analysis was used to confirm expression of Cx26, Cx40 and Cx43. The effect of visfatin (10-200ng/mL) on TGF-β1 secretion was confirmed by ELISA, and the effects of both TGF-β1 (2-10ng/mL) and visfatin (10-200ng/mL) on connexin expression were assessed by western blot. Functional intercellular communication was determined using transfer of Lucifer Yellow and paired-whole cell patch clamp electrophysiology. Results: In low glucose (5mM), visfatin (10-200ng/mL) did not affect membrane integrity, cytotoxicity or cell viability at 48hrs, but did evoke a concentration-dependent reduction in Cx26 and Cx43 expression. The expression of Cx40 was unaffected. At 48hrs, visfatin (10-200ng/mL) increased the secretion of TGF-β1 and the visfatin-evoked changes in connexin expression were mimicked by exogenous application of the pro-fibrotic cytokine (2-10ng/ml). Visfatin reduced dye transfer between coupled cells and decreased functional conductance, with levels falling by 63% as compared to control. Although input resistance was increased following visfatin treatment by 166%, the change was not significant as compared to control. The effects of visfatin on Cx-expression and cell-coupling were blocked in the presence of a TGF-β1 specific neutralizing antibody. Conclusions: The adipocytokine visfatin selectively evoked a non-toxic reduction in connexin expression in HK2-cells. The loss in gap-junction associated proteins was mirrored by a loss in functional conductance between coupled cells. Visfatin increased TGF-β secretion and the pattern of change for connexins expression was mimicked by exogenous application of TGF-β1. The effect of visfatin on Cx-expression and dye transfer were negated in the presence of a TGF-β1 neutralising antibody. These data suggest that visfatin reduces connexin-mediated intercellular communication in proximal tubule-derived epithelial cells via a TGF-β dependent pathway.

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“…Функция ренинового аппарата почек обеспечивается скоординированной активностью юкстагломерулярных клеток, клеток macula densa и экстрагломерулярного мезангиума. Несмотря на то, что молекулярные механизмы межклеточных взаимодействий, контролирующих высвобождение ренина, изучены недостаточно, известно, что ведущее место в этих процессах принадлежит белкам-коннексинам (Сх) [7]. Собранные в виде гексамерного коннексона, они образуют трансмембранный гемиканал для паракринной передачи сигналов, либо стыкуются с коннексонами на соседних клетках, создавая щелевое соединение для передачи метаболических и электрических сигналов [21].…”

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Clinical Aspects of Connexins 37, 40, 43, 45 Expression in the Embryonic and Adult Kidneys

Shapovalova,

Kutuzova,

Vasilenko

et al. 2023

Žurnal anatomii i gistopatologii

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Nowdays, there is a wide variety of judgments regarding the specific expression of some forms of connexins (Cx) in the renin apparatus of the embryonic and adult kidneys. Establishing the exact intrarenal localization of Cx 40, 37, 43, 45 is a prerequisite for understanding their functional role in normal renal organogenesis, as well as in maintaining fluid homeostasis and controlling renin secretion. At 8–10 weeks of embryonic development, the expression of various Cx is observed in the epithelium of blood vessels and renal tubules, as well as in the region of the renal renin apparatus, but with different patterns of expression and intensity over time. During embryogenesis, the expression of Cx 40 is higher than that of Cx 43, 37, and 45. In the postnatal period, the expression of Cx 40 decreases, while the expression of others increases. Cx 40 is involved in the formation of the renin apparatus in the developing kidney, while Cx 37, Cx 43, and Cx 45 are involved in signaling important for postnatal maintenance of kidney function and blood pressure control. Knockout Cx 45 is a lethal mutation that leads to impaired differentiation of smooth muscle tissue of arterioles. On the contrary, the deletion of individual genes Cx 37, 40 and 43 has little effect on renal organogenesis, probably due to the redundancy and interchangeability of various connexin isoforms. Experimental studies in the adult kidney demonstrate that arterial endothelial cells express Cx 40 and Cx 37 and, to a lesser extent, Cx 43, while smooth muscle cells express Cx 45. The cells of the renin apparatus are characterized by the expression of Cx 37, Cx 40, Cx 43 and Cx 45, with the highest content of Cx 40, especially in juxtaglomerular cells. Adequate and coordinated work of Cx is crucial for the regulation of renal hemodynamics and renin secretion in nephrology. The use of specific connexin-mimetic peptides may lead to the development of more effective methods for controlling renin secretion.

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Minding the Gap

Cited by 3 publications

References 18 publications

Classical Renin‐Angiotensin System in Kidney Physiology

Classical Renin‐Angiotensin System in Kidney Physiology

Visfatin Reduces Gap Junction Mediated Cell-to-Cell Communication in Proximal Tubule-Derived Epithelial Cells

Clinical Aspects of Connexins 37, 40, 43, 45 Expression in the Embryonic and Adult Kidneys

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