Role of apoptosis in development of the ascending thin limb of the loop of Henle in rat kidney

Kim, J.; Lee, G. S.; Tisher, C. Craig; Madsen, Kirsten

doi:10.1152/ajprenal.1996.271.4.f831

Cited by 41 publications

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“…3O arrow). This physiological apoptosis plays an essential role in the generation of the thin ascending limb of the mature HL, which first appears just after birth in rat kidneys (Kim et al, 1996). In Brn1 -/-kidneys lacking immature loops (Fig.…”

Section: Elongation Of Hls Was Severely Retarded In Homozygous Brn1-mmentioning

confidence: 94%

Crucial roles of Brn1 in distal tubule formation and function in mouse kidney

et al. 2003

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This study identifies a role for the gene for the POU transcription factor Brn1 in distal tubule formation and function in the mammalian kidney. Normal development of Henle's loop (HL), the distal convoluted tubule and the macula densa was severely retarded in Brn1-deficient mice. In particular, elongation and differentiation of the developing HL was affected. In the adult kidney, Brn1 was detected only in the thick ascending limb (TAL) of HL. In addition, the expression of a number of TAL-specific genes was reduced in the Brn1 +/-kidney, including Umod, Nkcc2/Slc12a1, Bsnd, Kcnj1 and Ptger3. These results suggest that Brn1 is essential for both the development and function of the nephron in the kidney.

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Section: Elongation Of Hls Was Severely Retarded In Homozygous Brn1-mmentioning

confidence: 94%

Crucial roles of Brn1 in distal tubule formation and function in mouse kidney

et al. 2003

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“…Consistent with this notion, the renal medulla separates into an outer and inner zone only after birth (3). This separation is realized by differentiation of loops of Henle leading to formation of thin limbs via coordinated cell proliferation and selective apoptosis (4,8). Local hypertonicity and cell shrinkage may be important factors controlling apoptosis in the developing kidney, but their role in the developmental differentiation of the kidney medulla is presently unexplored.…”

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confidence: 99%

Hypertonicity and TonEBP promote development of the renal concentrating system

Kültz¹

2004

American Journal of Physiology-Renal Physiology

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DESPITE SEVERE HYPEROSMOTIC stress imposed by NaCl and urea on cells of the renal medulla, the elevated and highly variable osmolality in this part of the kidney is necessary for proper function of the urinary concentrating mechanism. This mechanism develops only after birth, and newborn rats are incapable of producing concentrated urine (13). Depending on hydration state, renal medullary osmolality of adult rats ranges from 500 to Ͼ2,500 mosmol/kgH 2 O as a result of elevated salt and urea concentrations. Although increases in salt and urea both lead to hyperosmolality, only increased salt concentration causes hypertonicity (leading to cell shrinkage). The reason for this difference between salt and urea is the high membrane permeability of urea, which is mostly comparable to that of water. Consequently, urea and salt have different effects on kidney cells. In this issue of AJP-Renal Physiology, Han and coworkers (6) show that hypertonicity in the renal medulla represents an important signal for medullary differentiation and development of the urinary concentrating mechanism.Over the years, remarkable progress has been made in our understanding of how kidney cells adapt to the stress of hypertonicity. Cellular accumulation of organic osmolytes such as inositol, betaine, and sorbitol represents a central feature of adaptation to hypertonic stress. Organic osmolytes are compatible with cell function and protect renal cells from deleterious effects of hypertonicity by lowering intracellular ionic strength (2). The transcription factor tonicity-responsive enhancer binding protein (TonEBP) plays a key role in the accumulation of organic osmolytes by stimulating gene expression of membrane transporters (sodium-inositol cotransporter and sodium-chloride-betaine cotransporter) and a biosynthetic enzyme (aldose reductase) that catalyzes production of sorbitol from glucose (14). Interestingly, TonEBP also stimulates transcription of genes encoding vasopressin-activated urea transporters (UT-A1 and UT-A3) in inner medullary collecting duct cells, suggesting that TonEBP contributes to urea accumulation in renal medullary interstitium (12). In addition, TonEBP stimulates expression of the heat shock protein HSP70, which in turn protects proteins from the denaturing effects of urea (15). These wide-ranging transcriptional targets delineate TonEBP as a critical element of osmosensory signal transduction in cells of the renal medulla.The article by Han et al. (6) provides insight into how TonEBP contributes to development of urinary concentrating ability by analysis of expression of TonEBP and its target genes in developing rat kidney. TonEBP expression is first detected in the renal medulla at the fetal age of 16 days. It increases slowly through birth until postnatal day 21, when the renal medulla is fully developed and maximal urinary concentrating ability is achieved. Han et al. observe that, in general, expression of TonEBP in the kidney precedes that of its target genes, such as the sodium-inositol cotransporter, aldose ...

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“…Kim et al (4) reported that the cuboidal epithelium of the TAL of the renal papilla is gradually transformed into the ATL during the first 2 weeks of life. However, despite this study, little is currently known about a trigger for this structural change.…”

Section: Discussionmentioning

confidence: 99%

Gestational Length Affects a Change in the Transepithelial Voltage and the rNKCC2 Expression Pattern in the Ascending Thin Limb of Henle's Loop

et al. 2007

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ABSTRACT:To examine whether the functional and morphologic conversion of the neonatal ascending thin limb (ATL) of Henle's loop is related to gestational length, we evaluated the transepithelial voltages (Vts) of ATLs in perinatal mouse, hamster, rabbit, and rat kidneys. In isolated microperfused tubule preparations, Vts of neonatal ATLs were 23.8 Ϯ 1.4 in mouse, 25.7 Ϯ 2.2 in hamster, and 18.2 Ϯ 1.6 mV in rabbit. The influence of gestational length on the Vts and rat Na-K-Cl cotransporter (rNKCC2) expression pattern was also examined in perinatal rats subjected to a prolonged gestation due to either a daily s. M ammalian neonates possess a nearly mature urinediluting ability at birth (1); however, human neonates are unable to produce hypertonic urine at concentrations Ͼ400 mOsmol/kg, and rats are unable to produce hypertonic urine Ͼ600 mOsmol/kg. These observations indicate that the urineconcentrating ability is quite immature at birth (2). A number of researchers have tried to determine why the urineconcentrating ability of neonates does not reach adult levels; however, none have succeeded in explaining this phenomenon.It was first reported in the 19th century that morphologically, neonatal kidneys do not possess inner medullae (3). Subsequently, Kim et al. (4) clarified the subject by reporting that the ATL of Henle's loop of neonatal rats is also morphologically different from that of adults. They reported that the ATL in the neonatal period is very similar to the thick ascending limb (TAL) and that the tubule is replaced by the mature ATL cells after apoptosis and transformation.In an attempt to clarify the urine-concentrating mechanism in the neonatal period, we examined the renal tubular function directly in a series of experiments using in vitro tubule microperfusion technique and measured mRNAs for wellknown transporters and channels in the isolated inner medullary tubules of fetal, neonatal, and adult rat kidney (5). Our results led to a striking new concept regarding the maturating mechanism for the urine concentrating ability of mammalian neonates. We demonstrated that the renal medullary tubule organization of neonatal rats shares a marked similarity to the avian renal medulla. We postulate that the neonatal period is a phase of functional conversion of the urine concentrating mechanism from avian type to the mammalian type.In mammals, a urine-concentrating mechanism that is more dependent on urea than NaCl is the major protective response to a dry environment. In birds, both regulation of glomerular filtration and a urine-concentrating mechanism that is dependent on NaCl play important roles in fluid and electrolyte homeostasis. From the phylogenetic perspective, the urineconcentrating mechanism is unique in that it is only present in the metanephros of birds and mammals. Urine-concentrating ability develops after birth and matures during the weaning period.Changes in the renal medullary tubular transport properties of mature quail (6 -9), neonatal rats, and mature rats were compared in our previo...

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Role of apoptosis in development of the ascending thin limb of the loop of Henle in rat kidney

Cited by 41 publications

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Crucial roles of Brn1 in distal tubule formation and function in mouse kidney

Crucial roles of Brn1 in distal tubule formation and function in mouse kidney

Hypertonicity and TonEBP promote development of the renal concentrating system

Gestational Length Affects a Change in the Transepithelial Voltage and the rNKCC2 Expression Pattern in the Ascending Thin Limb of Henle's Loop

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