Aldosterone treatment of M1-CCD cells stimulated an increase in epithelial Na(+) channel (ENaC) alpha-subunit expression that was mainly localized to the apical membrane. PKD1-suppressed cells constitutively expressed ENaCalpha at low abundance, with no increase after aldosterone treatment. In the PKD1-suppressed cells, ENaCalpha was mainly localized proximal to the basolateral surface of the e...

Protein kinases are of particular interest in treatment of human diseases because of their enzymatic activity and susceptibility to successful therapeutic targeting. Protein kinase D1 (PKD1), cloned from humans and mouse by two different groups and reported simultaneously in 1990s, is emerging as a protein of translational value. Accumulating evidence in the literature demonstrate that PKD1 pla...

BACKGROUND The homozygous deletion of Pkd1 in the mouse results in embryonic lethality with renal cysts and hydrops fetalis, but there is no precise data on the segmental origin of cysts and potential changes associated with polyhydramnios. METHODS We used Pkd1-null mice to investigate cystogenesis and analyze the amniotic fluid composition from embryonic day 12.5 (E12.5) to birth (n = 257 em...

Despite their role in resolving inflammatory insults, neutrophils trigger inflammation-induced acute lung injury (ALI), culminating in acute respiratory distress syndrome (ARDS), a frequent complication with high mortality in humans. Molecular mechanisms underlying recruitment of neutrophils to sites of inflammation remain poorly understood. Here, we show that p38 MAP kinase p38δ is required fo...

Specification of the mammalian left–right (L–R) axis is controlled by fluid flows in the embryonic node, a ciliated pit like structure located at the distal tip of the mouse embryo. Nodal cilia rotate so as to cause a leftward fluid flow-this has been experimentally demonstrated to control embryonic sidedness. How the embryo interprets this flow remains the subject of debate. The two cilia hypo...

Specification of the mammalian left–right (L–R) axis is controlled by fluid flows in the embryonic node, a ciliated pit like structure located at the distal tip of the mouse embryo. Nodal cilia rotate so as to cause a leftward fluid flow-this has been experimentally demonstrated to control embryonic sidedness. How the embryo interprets this flow remains the subject of debate. The two cilia hypo...

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenetic disease predominantly caused by alteration or dysregulation of the PKD1 gene, which encodes polycystin-1 (PC1). The disease is characterized by the progressive expansion of bilateral fluid-filled renal cysts that ultimately lead to renal failure. Individual cysts, even within patients with germline mutations, ar...

The invariant asymmetric placement of thoracic and abdominal organs in the vertebrates is controlled by the left-asymmetric activity of the Nodal signaling cascade during embryogenesis. In the mouse embryo asymmetric induction of nodal is thought to be dependent on functional monocilia on the ventral node cells and on the Pkd2 gene, which encodes the calcium channel polycystin-2 (PC2). In human...

BACKGROUND The major gene mutated in autosomal dominant polycystic kidney disease was first identified over 20 years ago, yet its function remains poorly understood. We have used a systems-based approach to examine the effects of acquired loss of Pkd1 in adult mouse kidney as it transitions from normal to cystic state. METHODS We performed transcriptional profiling of a large set of male and ...

BACKGROUND/AIMS Cystic epithelia in polycystic kidney disease display features similar to malignant cells. Thiazolidinediones have been shown to have anti-neoplastic properties, therefore we tested the hypothesis that pioglitazone reduces cyst formation, improves renal function, and prolongs survival in a mouse model of polycystic kidney disease. METHODS PC-Pkd1-KO mice, which have homozygous...