Publications by authors named "Jayalakshmi Lakshmipathi"

Loss of nephron primary cilia due to disruption of the Ift88 gene results in sex- and age-specific phenotypes involving renal cystogenesis, blood pressure (BP) and urinary Na excretion. Previous studies demonstrated that male mice undergoing induction of nephron-specific Ift88 gene disruption at 2 months of age developed reduced BP and increased salt-induced natriuresis when pre-cystic (2 months post-induction) and became hypertensive associated with frankly cystic kidneys by 9 months post-induction; in contrast, female Ift88 KO mice manifested no unique phenotype 2 months post-induction and had mildly reduced BP 9 months post-induction. The current study utilized these Ift88 KO mice to investigate associated changes in renal Na transporter and channel protein expression.

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Background: Primary cilia regulation of renal function and BP in health and disease is incompletely understood. This study investigated the effect of nephron ciliary loss on renal physiology, BP, and ensuing cystogenesis.

Methods: Mice underwent doxycycline (DOX)-inducible nephron-specific knockout (KO) of the gene at 2 months of age using a Cre-LoxP strategy.

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Background: The physiologic role of renomedullary interstitial cells, which are uniquely and abundantly found in the renal inner medulla, is largely unknown. Endothelin A receptors regulate multiple aspects of renomedullary interstitial cell function .

Methods: To assess the effect of targeting renomedullary interstitial cell endothelin A receptors , we generated a mouse knockout model with inducible disruption of renomedullary interstitial cell endothelin A receptors at 3 months of age.

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Background: Hypertension often occurs before renal function deteriorates in autosomal dominant polycystic kidney disease (ADPKD). It is unknown whether the gene product polycystin-1-the predominant causal factor in ADPKD-itself contributes to ADPKD hypertension independent of cystogenesis.

Methods: We induced nephron-specific disruption of the gene in 3-month-old mice and examined them at 4-5 months of age.

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Failure to expand pancreatic β-cells in response to metabolic stress leads to excessive workload resulting in β-cell dysfunction, dedifferentiation, death, and development of type 2 diabetes. In this study, we demonstrate that induction of Myc is required for increased pancreatic β-cell replication and expansion during metabolic stress-induced insulin resistance with short-term high-fat diet (HFD) in young mice. β-Cell-specific Myc knockout mice fail to expand adaptively and show impaired glucose tolerance and β-cell dysfunction.

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The inner medullary collecting duct (IMCD) produces very high levels of endothelin-1 (ET-1) that acts as an autocrine inhibitor of IMCD Na and water reabsorption. Recent studies suggest that IMCD ET-1 production is enhanced by extracellular hypertonicity as can occur during high salt intake. Although NFAT5 has been implicated in the IMCD ET-1 hypertonicity response, no studies in any cell type have identified NFAT5 as a transcriptional regulator of the EDN1 gene; the current study examined this using a mouse IMCD cell line (IMCD3).

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The collecting duct is the predominant nephron site of prorenin and prorenin receptor (PRR) expression. We previously demonstrated that the collecting duct PRR regulates epithelial Na channel (ENaC) activity and water transport; however, which cell type is involved remains unclear. Herein, we examined the effects of principal cell (PC) or intercalated cell (IC) PRR deletion on renal Na and water handling.

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Adaptive β-cell replication occurs in response to increased metabolic demand during insulin resistance. The intracellular mediators of this compensatory response are poorly defined and their identification could provide significant targets for β-cell regeneration therapies. Here we show that glucose and insulin in vitro and insulin resistance in vivo activate protein kinase C ζ (PKCζ) in pancreatic islets and β-cells.

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Insulin resistance, when combined with decreased β-cell mass and relative insufficient insulin secretion, leads to type 2 diabetes. Mice lacking the IRS2 gene (IRS2(-/-) mice) develop diabetes due to uncompensated insulin resistance and β-cell failure. Hepatocyte growth factor (HGF) activates the phosphatidylinositol 3-kinase/Akt signaling pathway in β-cells without recruitment of IRS1 or IRS2 and increases β-cell proliferation, survival, mass, and function when overexpressed in β-cells of transgenic (TG) mice.

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