Optical Clearing in the Kidney Reveals Potassium-Mediated Tubule Remodeling

Puelles, Victor G.; Su, Xiao Tong; McCormick, James A.; Welling, Paul A.; Ellison, David H.

doi:10.1016/j.celrep.2018.11.021

Cited by 46 publications

(41 citation statements)

References 32 publications

(59 reference statements)

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“…The changes in NCC by a low-K ϩ diet have been linked to decreased natriuresis, kaliuresis, and increased blood pressure, which could be corrected by administration of a thiazide diuretic (319,354). Of interest, dietary K ϩ restriction also increased cell proliferation in various nephron segments, including DCT1 (FIGURE 5A) (279).…”

Section: Low K ϩ Mediates Phosphorylation Of Nccmentioning

confidence: 97%

“…The DCT is a short segment of the nephron starting immediately after the unique cells of the macula densa (307). The length of the DCT is~0.6 -0.7 mm in adult mice (279,402), 1 mm in adult rats (70), and 5 mm in humans (45,307). DCT cells are characterized by microprojections on their luminal surface, an apically positioned nucleus, and extensive basolateral invaginations and lateral interdigitations (185).…”

Section: The Dctmentioning

confidence: 99%

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Regulation of the Renal NaCl Cotransporter and Its Role in Potassium Homeostasis

Hoorn

Gritter

Cuevas³

et al. 2020

Physiological Reviews

118

137

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Daily dietary potassium (K+) intake may be as large as the extracellular K+ pool. To avoid acute hyperkalemia, rapid removal of K+ from the extracellular space is essential. This is achieved by translocating K+ into cells and increasing urinary K+ excretion. Emerging data now indicate that the renal thiazide-sensitive NaCl cotransporter (NCC) is critically involved in this homeostatic kaliuretic response. This suggests that the early distal convoluted tubule (DCT) is a K+ sensor that can modify sodium (Na+) delivery to downstream segments to promote or limit K+ secretion. K+ sensing is mediated by the basolateral K+ channels Kir4.1/5.1, a capacity that the DCT likely shares with other nephron segments. Thus, next to K+-induced aldosterone secretion, K+ sensing by renal epithelial cells represents a second feedback mechanism to control K+ balance. NCC’s role in K+ homeostasis has both physiological and pathophysiological implications. During hypovolemia, NCC activation by the renin-angiotensin system stimulates Na+ reabsorption while preventing K+ secretion. Conversely, NCC inactivation by high dietary K+ intake maximizes kaliuresis and limits Na+ retention, despite high aldosterone levels. NCC activation by a low-K+ diet contributes to salt-sensitive hypertension. K+-induced natriuresis through NCC offers a novel explanation for the antihypertensive effects of a high-K+ diet. A possible role for K+ in chronic kidney disease is also emerging, as epidemiological data reveal associations between higher urinary K+ excretion and improved renal outcomes. This comprehensive review will embed these novel insights on NCC regulation into existing concepts of K+ homeostasis in health and disease.

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Section: Low K ϩ Mediates Phosphorylation Of Nccmentioning

confidence: 97%

Section: The Dctmentioning

confidence: 99%

Regulation of the Renal NaCl Cotransporter and Its Role in Potassium Homeostasis

Hoorn

Gritter

Cuevas³

et al. 2020

Physiological Reviews

118

137

View full text Add to dashboard Cite

show abstract

“…Chronic hypokalemia leads to renal hypertrophy and to the so called hypokalemic nephropathy, a type of interstitial nephritis affecting mainly the medullary segments of the kidneys 13,14 . Tubular remodeling already starts after 3 days of KD diet and involves mainly the proximal and distal convoluted tubule, and the CD as demonstrated by optical clearing techniques 15 .…”

Section: Discussionmentioning

confidence: 99%

Potassium depletion induces cellular conversion in the outer medullary collecting duct altering Notch signaling pathway

Iervolino

Prosperi

Motte

et al. 2020

Sci Rep

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Potassium depletion affects AQP2 expression and the cellular composition of the kidney collecting duct. This, in turn, contributes to the development of a secondary form of nephrogenic diabetes insipidus and hypokalemic nephropathy. Here we show that after 14 days of potassium depletion, the cellular fraction of A-type intercalated cells increases while the fraction of principal cells decreases along the outer medullary collecting duct in rats. The intercalated cells acquired a novel distribution pattern forming rows of cells attached to each other. These morphological changes occur progressively and reverse after 7 days of recovery on normal rat chow diet. The cellular remodeling mainly occurred in the inner stripe of outer medulla similar to the previously seen effect of lithium on the collecting duct cellular profile. The cellular remodeling is associated with the appearance of cells double labelled with both specific markers of principal and type-A intercalated cells. The appearance of this cell type was associated with the downregulation of the Notch signaling via the Hes1 pathways. These results show that the epithelium of the collecting duct has a high degree of plasticity and that Notch signaling likely plays a key role during hypokalemia.

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“…They called the new formula 2ECi, 2nd generation ethyl cinnamate–mediated clearing. Application of ECi has already allowed the researchers to visualize morphological and molecular remodeling of distal convoluted tubules upon low‐potassium diet and to reveal new 3D quantitative endpoints in the model of crescentic nephritis . ECi‐based clearing was also applied to present utility of new cationic near infrared fluorescent agent, MHI148‐PEI, for specific staining of vascular structures in variety of organs, for example, skin, liver and lung .…”

Section: Application Of Toc For Particular Peripheral Organsmentioning

confidence: 99%

Advances in Ex Situ Tissue Optical Clearing

Matryba

Kaczmarek

Gołąb

2019

Laser & Photonics Reviews

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Examination of whole organs with subcellular resolution in health, disease, and during development is necessary to decipher their biological complexity. However, until recently, this has been virtually impossible due to the natural opacity of organ tissue. Recent progress in tissue optical clearing (TOC) has overcome this limitation by turning organs into transparent, light-permitting specimens. At least 20 original TOC methods have been developed in less than a decade, which were followed by hundreds of attempts that were aimed at their optimization and practical application. The majority of proof-of-concept studies have focused on the brain. However, it is apparent that TOC might be equally valuable when applied to peripheral organs or even the whole body. The progress in TOC for peripheral organs is delineated in an organ-by-organ fashion and whole-body clearing approaches are discussed. Additionally, physical and optical approaches for TOC affecting the optical properties of the samples and image quality are discussed to explore their advantages, limitations, and future possibilities.

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Optical Clearing in the Kidney Reveals Potassium-Mediated Tubule Remodeling

Cited by 46 publications

References 32 publications

Regulation of the Renal NaCl Cotransporter and Its Role in Potassium Homeostasis

Regulation of the Renal NaCl Cotransporter and Its Role in Potassium Homeostasis

Potassium depletion induces cellular conversion in the outer medullary collecting duct altering Notch signaling pathway

Advances in Ex Situ Tissue Optical Clearing

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