Cyst Lumen Research Articles

Ovarian Cysts in MRL/MpJ Mice Originate from Rete Ovarii

In MRL mice aged more than 1 year, but not in C57BL/6 mice, ovaries had grossly visible cysts presenting unilaterally or bilaterally. Postnatally, all MRL mice developed ovarian cysts by 8 months of age. Observations by light microscopy, including lectin histochemistry, indicated that the cysts sometimes included papillomatous tissues located at the hilar region and were similar to the rete ovarii system, but not to follicles. Two types of epithelial cells, ciliated and non-ciliated, were arranged on the cysts, in which both cell types had many microvilli projecting in various directions and random ramifications in the cystic lumen. These characteristics suggest that ovarian cysts developing in MRL mice originate mostly from the rete ovarii. Cysts derived from the rete ovarii at 8 months of age were histologically detected in all C3H mice as well as MRL mice, with variable incidence in ICR, AKR, CBA/N and ddY, and none in C57L/6, DBA/2, BALB and A/J mice. However, measurement of the maximum diameters of the ovarian cysts indicated that MRL mice regularly possessed the largest cysts visible to the naked eye. This is the first report of ovarian cysts in this inbred strain, suggesting that ovarian cysts in MRL mice appear with stable incidence and development.

Regulated ion transport in mouse liver cyst epithelial cells

Derived from bile duct epithelia (BDE), secretion by liver cyst-lining epithelia is positioned to drive cyst expansion but the responsible ion flux pathways have not been characterized. Cyst-lining epithelia were isolated and cultured into high resistance monolayers to assess the ion secretory pathways. Electrophysiologic studies showed a marked rate of constitutive transepithelial ion transport, including Cl − secretion and Na + absorption. Na + absorption was amiloride-sensitive, suggesting the activation of epithelial sodium channels (ENaC). Further, both cAMP i and extracellular ATP induced robust secretory responses. Western blotting and immunohistologic analysis of liver cyst epithelia demonstrated expression of P2X4, a potent purinergic receptor in normal BDE. Luminometry and bioassaying measured physiologically relevant levels of ATP in a subset of liver cyst fluid samples. Liver cyst epithelia also displayed a significant capacity to degrade extracellular ATP. In conclusion, regulated ion transport pathways are present in liver cyst epithelia and are positioned to direct fluid secretion into the lumen of liver cysts and promote increases in liver cyst expansion and growth.

Foregut Cyst of the Oesophageal Wall in a Cynomolgus Monkey (Macaca fascicularis)

Congenital oesophageal cysts of foregut origin are rare in animals and human beings. This report describes a case in a 4-year-old cynomolgus monkey with no clinical symptoms. The cyst, which was located within the oesophageal submucosal tissue near the mid-point of the oesophagus, was lined with pseudostratified ciliated epithelium and had a thin layer of submucosal tissue. The cyst was surrounded by a smooth muscle layer which was partly intermingled with the circular muscle layer of the oesophagus. The muscularis mucosae of the oesophagus was not shared with the cyst wall. Simple tubular glands were present, opening into the cyst lumen. No communication between the cyst lumen and the oesophagus was observed. Cartilaginous tissue, which is a diagnostic feature of bronchogenic cysts, was not identified in the cyst wall. On the basis of the histopathological features, a foregut cyst of the oesophagus was diagnosed.

Macrophages in human fallopian tube and ovarian epithelial inclusion cysts

Epithelial inclusion cysts (EICs) are considered a preferential site for ovarian carcinogenesis. Local inflammation, associated to ovulatory wound repair and epithelial inflammatory conditions, facilitates EIC formation and involves activation of macrophages. The aim of this study was to analyse the presence and numbers of macrophages in the ovarian surface epithelium (OSE), in EICs, and in the fallopian tubes, as tubal metaplasia is a common finding in EICs. Immunohistochemical analysis of macrophages was performed in 25 fallopian tubes in different phases of the menstrual cycle, and in 30 ovaries showing EICs from cycling and postmenopausal women. In the fallopian tube, macrophages were abundant and underwent cyclic changes during the menstrual cycle, being particularly abundant within the epithelium at early and mid-luteal phases. Macrophages were not found in the normal OSE. However, OSE areas and EICs showing tubal metaplasia were invariably associated with infiltration by abundant macrophages. Macrophages were present among epithelial cells, infiltrating the cyst wall, as well as free in the cyst lumen. No significant differences existed between follicular and luteal phases of the cycle, or between cycling and postmenopausal women. This study has demonstrated that macrophages are associated with metaplastic EICs, and raises the possibility that these cells contribute to the particular microenvironment of EICs through secretion of cytokines and growth factors that may reach bioactive concentrations in the confined space of the EICs.

Antagonism of endogenous putative P2Y receptors reduces the growth of MDCK-derived cysts cultured in vitro

P2Y receptors couple to G proteins and either mobilize intracellular Ca(2+) or alter cAMP levels to modulate the activity of Ca(2+)- and cAMP-sensitive ion channels. We hypothesize that increased ion transport into the lumen of MDCK cysts can osmotically drive fluid movement and increase cyst size. Furthermore, activation of the adenylate cyclase/cAMP pathway may trigger cell proliferation via an extracellular signal-related kinase cascade. To test this hypothesis, several P2Y receptor inhibitors were used on the MDCK in vitro model of renal cyst formation. The nonspecific P2 receptor inhibitors reactive blue 2 and suramin reduced cyst growth significantly, as did PPADS and, to a lesser extent, the P2Y(1)-specific antagonist MRS2179. Cyst growth was reduced by approximately 50% when ATP was removed from the culture medium with apyrase, although stable analogs of ATP failed to increase cyst size. The nonselective P2X receptor inhibitor Coomassie brilliant blue G was ineffective at reducing cyst growth, suggesting no involvement of P2X receptors. Finally, the presence of selective inhibitors of ERK activation (either PD98059 or U0126) greatly reduced cyst growth, whereas in untreated cysts ERK activity was observed to increase with time. We conclude that stimulation of endogenous P2Y receptors by extracellular ATP increases growth of MDCK cysts via cAMP-dependent activation of the ERK pathway. P2Y receptor antagonists may have therapeutic potential in reducing cyst size and slowing disease progression; although further studies in vitro and in vivo are needed to investigate the specificity and role of these P2Y receptors in renal cystic diseases.

Florid cystic endosalpingiosis of the spleen

A case of endosalpingiosis appearing as a huge multilocular cyst in the spleen of a 31-year-old woman is reported. The cystic lumens were smooth, and lined by fallopian tubal epithelium containing ciliated and secretory cells. The epithelial lining showed neither atypia nor foci of papillary proliferation, with only 3-5% MIB-1 labeling index. The epithelial lining was histochemically negative for mucin, but positive for MUC1 and progesterone receptor. Despite the appearance of a tumor-like mass, it was diagnosed as florid cystic endosalpingiosis as there was a normal tube-like epithelium. Regarding etiology, it was considered to derive from the secondary müllerian system of the splenic capsule.

Scanning Electron Microscopic Study of the Nasolabial Cyst: Its Clinical and Embryological Implications

Nasolabial cyst is an uncommon midfacial cyst. It is considered to be a developmental anomaly arising from the rest of nasal respiratory epithelium. Although the cyst is a well-recognized entity, there remains some confusion of its origin, cell types, and ultrastructures. Based on the routine light microscopic study, some authors reported the epithelial cells of the inner lining of the nasolabial cyst were ciliated; some others reported they were nonciliated. To clarify this, a scanning electron microscopic study is needed. This was a prospective clinical series. A transnasal marsupialization method was used to treat 10 patients with nasolabial cyst. With patients under local anesthesia, the roof of the cyst wall and a disk of nearby nasal mucosa were excised together with a sickle knife and scissors. Surgical specimens were dissected and processed for scanning electron microscopy and histochemistry. Patients were followed up for 8 to 65 months. Marsupialization of cysts was successfully performed on all patients. Electron microscopically, the inner surface of the nasolabial cysts in all the cases was lined with nonciliated columnar epithelium consisting chiefly of goblet cells and basal cells. It is suggested that goblet cells contributed to clear, thin, and yellow mucus present in the cyst lumen. Instead of cilia, these epithelial cell surfaces were equipped with numerous short, globular, or irregular microvilli. Apical cytoplasm of adjacent cells did not tightly adhere to each other. Instead, microsulci of 1 to 3 microm in width formed between cells. Cytoplasmic processes from the lateral border spanned the microsulcus and contacted with those from neighboring cells. The novel study has proved that the lining epithelium on the inner surface of the nasolabial cyst is columnar epithelium that chiefly consisted of two types of cells: goblet cells and basal cells. Not present were ciliated cells that were essential in the other portion of the respiratory tract. Numerous microvilli, instead of cilia, covered the inner lining of the nasolabial cyst, probably as a result of lacking the stimulation of air in ventilation as that on the other portion of the respiratory tract. The cilia of the epithelium were ill developed.

A Regulatory Role of Polycystin-1 on Cystic Fibrosis Transmembrane Conductance Regulator Plasma Membrane Expression

Autosomal dominant polycystic kidney disease(ADPKD) is caused by genetic mutations in eitherPKD1 or PKD2, the genes that encode polycystin-1(PC-1) and polycystin-2 (PC-2), respectively. ADPKDis characterized by the formation of multiple,progressive, fluid-filled renal cysts. To elucidate themechanism of fluid secretion by ADPKD cysts, weexamined the effect of PC-1 on the plasma membraneexpression of cystic fibrosis transmembraneconductance regulator (CFTR), a key Cl^- secretoryprotein. Five stably transfected MDCK lines were usedin this study: two transfected with empty vector (controlcells) and three expressing human PC-1 (PC-1 cells).The cAMP-induced endogenous short circuit currents(I_sc) were smaller in PC-1 cells than in control cells.Compared to control cells, PC-1 cells transientlyexpressing pEGFP-CFTR showed significantreduction of whole cell cAMP-activated Cl^- currents.Cell surface biotinylation experiments also indicateda reduction in surface expression of CFTR in PC-1cells compared to control. Furthermore, studies usingCHO cells transiently expressing PC-1 and CFTRsuggest the importance of the PC-1 COOH-terminusin the observed reduction of CFTR plasma membraneexpression. No differences in either endogeneous K⁺currents or P2Y receptor responses were observedbetween PC-1 and control cells, indicating thespecificity of PC-1’s action. These results indicate thatPC-1 selectively maintains low cell surface expressionof CFTR. Moreover, these findings suggest that themalfunction of PC-1 enhances plasma membraneexpression of CFTR, thus causing abnormal Cl^-secretioninto the cyst lumen.

Von Meyenburg complex associated with adult polycystic liver disease

The von Meyenburg complex (bile duct hamartoma) is a rare developmental disorder, manifested by multiple bile ducts. The polycystic liver disease is a rare congenital anomaly which may remain undiscovered until adult life, occurring more frequently in women. It is mostly asymptomatic, but sometimes surgical intervention is necessary. In the majority of cases, it is combined with cysts in the kidney and, rarely, in other organs as well. The cysts may vary in diameter from 1 mm to 20 cm, or even more. A 55-year-old woman underwent surgery based on clinical diagnosis: suspected Echinococcus liver cyst. Liver biopsy was performed, and a parenchymal tissue of 6.5x4x3 cm, with a cyst with a diameter of 2.5 cm, was resected. Within the cyst lumen there was a necrotic, mushy, yellow contents. Microscopically examined, it showed plenty of cholesterol crystals. The wall of the cyst consisted of hypocellular connective tissue. In the surrounding liver parenchyma, there were cystical formations of the same structure, measuring 1-2 mm. Also, there were some multiple bile duct hamartomas. The ducts were encircled by a delicate connective tissue. These changes correspond to von Meyenburg complex, i.e. biliary microhamartoma combined with adult polycystic disease. In our case, in the wall of the cyst there were numerous cholesterol crystals, pointing to its retention character and, probably, to the mechanism of its origin. After degeneration of biliary epithelium, the cyst wall grew very thick, due to proliferation of the connective tissue evoked by the aggressive chemical contents of the bile. Frequent development of cholangiocarcinoma within the cyst wall also points to long-term chemical irritation.

Mucous Retention Cyst of the Upper Lip Possibly Caused by Cavernous Hemangioma with Thrombi

The rare case of a mucous retention cyst in the upper lip, possibly caused by a cavernous hemangioma with thrombi, of a 74-year-old man is reported. Three mucous retention cysts were located under the suspected cavernous hemangioma with thrombi. The lumen of the largest cyst was lined with double-layered flattened epithelium and a few goblet-like cells ; the lumen of the other smaller cysts was lined with short columnar or cuboidal epithelium and no goblet-like cells. No other cause of duct obstruction was observed in the labial gland. In the present case, duct obstruction caused by a long-standing hemangioma apparently led to the formation of mucous retention cysts and the considerable retention of a mucous substance made the cyst larger, resulting in flattened epithelium.

The relationship between cell proliferation, Cl− secretion, and renal cyst growth: A study using CFTR inhibitors

In autosomal-dominant polycystic kidney disease (ADPKD), cAMP-stimulated cell proliferation and Cl- secretion via the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel drive the enlargement of fluid-filled epithelial cysts. To investigate how CFTR blockers inhibit cyst growth, we studied cAMP-dependent Cl- secretion, cell proliferation, and cyst growth using type I Madin Darby canine kidney (MDCK) cells as a model of renal cyst development and growth. We grew MDCK cysts in collagen gels in the presence of the cAMP agonist forskolin, measured Cl- secretion with the Ussing chamber technique, and assayed cell proliferation using nonpolarized and polarized MDCK cells. To inhibit CFTR, we used glibenclamide, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), genistein, and the specific CFTR inhibitor CFTRinh-172. As controls, we tested the effects of blockers of other types of apical membrane Cl- channels and inhibitors of basolateral membrane ion channels and transporters. In the absence of inhibitors of transepithelial ion transport, forskolin stimulated dramatic cyst growth. CFTR blockers and inhibitors of basolateral membrane ion channels and transporters retarded cyst growth. In contrast, blockers of other types of apical membrane Cl- channels, which were without effect on CFTR, failed to inhibit cyst growth. Inhibition of cyst growth by CFTR blockers was correlated with inhibition of cAMP-stimulated Cl- current (correlation coefficient = 0.81; P < 0.05), but not cell proliferation (correlation coefficient = 0.50; P > 0.05). Our data suggest that CFTR blockers might retard cyst growth predominantly by inhibiting fluid accumulation within the cyst lumen.

Endometriosis of the Pancreas Presenting as a Cystic Pancreatic Neoplasm with Possible Metastasis

The authors report a case of endometriosis that presented as a cystic mass in the tail of the pancreas, leading to extensive evaluation and ultimately a major surgical resection. The diagnosis was made by histopathological evaluation, revealing endometrial glands and stroma in the wall of the mass with hemorrhagic fluid in the cystic lumen, compatible with pancreatic involvement by an endometrial cyst.

On generation of statoconia in gravireceptors of mollusks

Two models of development of statoconia in the statocyst of mollusks, based on the experimental data [Hearing Res. 49 (1990) 63; Hearing Res. 109 (1997) 125; Hearing Res. 109 (1997) 109;] are proposed. The purpose of the present work is to apply mathematical modeling to the analysis of mechanisms of statoconia formation and generation by supporting cells at the stage of their accumulation in the cyst lumen. In the case of Aplysia californica, it is not clear whether there is a temporal change of statoconia due to their growth in the cyst lumen similar to that in Biomphalaria, or whether the growth of statoconia occurs in supporting cells before they get into the cyst lumen. This question has to do with a more general and insufficiently investigated problem of the mechanisms of statoconia evolution during their stage of accumulation. This is related to A. californica as well as to the initial phase of development of Biomphalaria glabrata. This problem is of practical importance because the majority of experiments related to the study of the effects of altered gravity on the development of gravireceptors in the two mollusks A. californica and B. glabrata deals with the initial phase of statoconia development. It is assumed that two main processes determine the evolution of statoconia in developing mollusks: generation of new statoconia by growing supporting cells and growth of statoconia sizes in the cyst lumen. Analysis of experimental data related to the generation of statoconia in Aplysia and comparison of these data with the results of modeling of accumulation of statoconia suggest that the basic mechanism of evolution of size distribution of statoconia in Aplysia is growth of embryonic statoconia in supporting cells, that follows the growth of animal size. Thus, the large sizes of statoconia are determined by their development within supporting cells rather than by their growth in the cyst lumen. Analysis of the data concerning Biomphalaria allows us to assume that distribution of supporting cells which generate statoconia also varies. The results of modeling of evolution of statoconia specify necessary additional experiments, which are required to refine and test the model.

Mucus retention cyst with development of basal cell adenoma: report of a case

<h3>Background</h3> Mucus retention cyst is a relatively uncommon lesion of the salivary gland. Unlike the more common mucus escape reaction, it is a true cyst that is lined by epithelium consisting of a uniform layer of cuboidal to low-columnar cells. However, a uniform thin layer of nonkeratinizing stratified squamous epithelium is common, and occasional mucous cells within the epithelial lining of the cyst can be observed. Some authors have mentioned that in some cases the epithelium demonstrates papillary folds into the cystic lumen, when these lesions are misdiagnosed as papillary cystadenoma. Other authors contend that mucus retention cysts do not show piling up of cells in the wall of the cyst and neither proliferation nor infiltration of islands of epithelium into the connective tissue is a feature. These histologic features with connection to the absence of multicystic structures and of areas of solid epithelial proliferations are particularly important to rule out cystic neoplasms. Also, in the literature review, we could not find any reported case of mucus retention cyst with development of a neoplasm from the lining epithelium. <h3>Case report</h3> A 68-year-old man was referred to the Department of Oral Medicine and Oral Pathology of the Aristotle University Dental School, Thessaloniki, Greece, because of a painless swelling that periodically fluctuated in size. Intraoral examination revealed a well demarcated mass, soft to palpation, measuring 1.5 × 1cm, located in the submucosa of the upper lip. The covered mucosa was reddish-blue in color. Under local anesthesia the lesion was totally excised. Histologic examination showed the presence of a monocystic lesion lined by atrophic epithelium in proximity to normal minor salivary glands. Islands consisting of single layered cuboidal or columnar epithelial cells were also observed in contact with the lining epithelium and floating into the cystic cavity. These cell islands, when examined immunohistochemically, reacted positively in keratin 7 and S-100 protein and negatively for vimentin. <h3>Conclusion</h3> The histologic and immunohistochemical findings supported diagnosis of mucus retention cyst with development of basal cell adenoma. Differential diagnosis of the tumor is discussed.

Study of the development and evolution of neointestine in a rat model

The implantation of fragmented rat intestinal epithelium into the omentum of syngeneic animals results in the formation of a cyst containing neointestine. The purpose of our project was to study the evolution of this neointestine-containing cyst over time. Harvested jejunum and ileum of neonatal DA rats (6 to 8 days old) was digested with collagenase type XI and dispase at room temperature. The resulting organoid units, containing clusters of intestinal epithelium with stem cells were seeded onto a polyglactin polymer mesh (100,000 units per mesh). The absorbable mesh was implanted in the omentum or peritoneal wall of an adult syngeneic animal. Animals were sacrificed at weekly intervals to harvest the neointestinal cysts. The lumen of the neointestine cysts was full of mucous while the wall of the cyst was covered by intestinal mucosa. H&E staining of the cyst demonstrated the morphology of intestinal epithelium; PAS staining identified goblet cells. The size of the cyst was maximal between 4 and 8 weeks postimplantation tending to regress thereafter. Neointestinal cysts are a consistent finding after implantation of intestinal epithelium organoids into the omentum or peritoneal wall in the rat model. The cysts reach a maximal size at 4 to 8 weeks postimplantation, tending to regress thereafter.

The Receptor Tyrosine Kinase Regulator Sprouty1 Is a Target of the Tumor Suppressor WT1 and Important for Kidney Development

WT1 encodes a transcription factor involved in kidney development and tumorigenesis. Using representational difference analysis, we identified a new set of WT1 targets, including a homologue of the Drosophila receptor tyrosine kinase regulator, sprouty. Sprouty1 was up-regulated in cell lines expressing wild-type but not mutant WT1. WT1 bound to the endogenous sprouty1 promoter in vivo and directly regulated sprouty1 through an early growth response gene-1 binding site. Expression of Sprouty1 and WT1 overlapped in the developing metanephric mesenchyme, and Sprouty1, like WT1, plays a key role in the early steps of glomerulus formation. Disruption of Sprouty1 expression in embryonic kidney explants by antisense oligonucleotides reduced condensation of the metanephric mesenchyme, leading to a decreased number of glomeruli. In addition, sprouty1 was expressed in the ureteric tree and antisense-treated ureteric trees had cystic lumens. Therefore, sprouty1 represents a physiologically relevant target gene of WT1 during kidney development.

Endoscopic ultrasound-guided drainage of pancreatic pseudocysts using a large-channel echoendoscope and a conventional polypectomy snare

Background: Endoscopic drainage of pancreatic pseudocysts is becoming common. Recent techniques using endoscopic ultrasound (EUS) have made the procedure safer and easier. However, bleeding related to the procedure is sometimes still experienced and placement of the tube is also sometimes difficult in cases where the cystic wall is thick and hard. We describe a new technique of EUS-guided drainage using a large-channel echoendoscope, a conventional polypectomy snare and a high-frequency current generator with automatic controls. We also evaluate this technique's utility. Methods: Between May 2001 and December 2002, EUS-guided drainage was attempted in consecutive patients with symptomatic pancreatic pseudocysts that had resisted conservative treatments. The EUS device was a recently introduced large-channel linear scanning echoendoscope. A puncture was made with a 19 G needle under EUS guidance and a 0.035 inch guidewire was passed through the puncture and into the pseudocyst. Then, a conventional polypectomy snare was used to enlarge the puncture tract with the new current generator, and a 7 Fr pigtail-type nasocystic drain was placed. Results: The drainage was successful and insertion of the drain was easy in all 13 patients included in the study. No complications related to the procedure, such as bleeding and perforation, were observed. The clinical symptoms resolved after the procedure in all patients. In nine patients, the cyst completely disappeared and the discharge also stopped, allowing the tube to be removed after a mean of 15 days. The median follow-up period for these nine patients was 4 months and no recurrence has been observed. In two other patients, the cysts shrank but did not disappear completely 4 weeks or more after the procedure. Since both of these patients had had previous cystic infections, they were given surgical operations. In the remaining two cases, the cystic lumen completely disappeared but the discharge continued for 4 weeks, so we replaced the 7 Fr nasobiliary tube with a 10 Fr internal drainage tube. Conclusion: This method is an easy and effective treatment for pancreatic pseudocysts. It may also reduce the risk of bleeding related to the procedure.

The isolated polycystin-1 cytoplasmic COOH terminus prolongs ATP-stimulated Cl- conductance through increased Ca2+ entry.

The precise steps leading from mutation of the polycystic kidney disease (PKD1) gene to the autosomal dominant polycystic kidney disease (ADPKD) phenotype remain to be established. Fluid accumulation is a requirement for cyst expansion in ADPKD, suggesting that abnormal fluid secretion into the cyst lumen might play a role in disease. In this study, we sought to establish a link between polycystin-1 (the PKD1 gene product) and ATP-stimulated Cl- secretion in renal tubule cells. To do this, we performed a whole cell patch-clamp analysis of the effects of expression of the isolated cytoplasmic COOH-terminus of polycystin-1 in stably transfected mouse cortical collecting duct cells. The truncated polycystin-1 fusion protein prolonged the duration of ATP-stimulated Cl- conductance and intracellular Ca2+ responses. Both effects were dependent on extracellular Ca2+. It was determined that expression of the truncated polycystin-1 fusion protein introduced, or activated, an ATP-induced Ca2+ entry pathway that was undetectable in transfection control cell lines. Our findings are concordant with increasing evidence for a role of polycystin-1 in cell Ca2+ homeostasis and indicate that dysregulated Ca2+ entry might promote Cl- secretion and cyst expansion in ADPKD.

The isolated C-terminus of polycystin-1 promotes increased ATP-stimulated chloride secretion in a collecting duct cell line

Cyst expansion in autosomal dominant polycystic kidney disease (ADPKD) requires accumulation of fluid into the cyst lumen, which is probably driven by aberrant chloride secretion by the cyst lining epithelium. Extracellular ATP is a potent stimulus for chloride secretion in many epithelial systems, and provides a plausible mechanism for secretion in ADPKD. Therefore the link between polycystin-1 and ATP-stimulated chloride secretion was investigated in the M1 cortical collecting duct cell line. M1 cells were stably transfected with a glucocorticoid-inducible cytoplasmic C-terminal polycystin-1 construct fused to a membrane expression cassette. Induction of fusion protein expression was associated with augmentation of ATP-stimulated transepithelial chloride secretion. After nystatin-induced permeabilization of the basolateral membrane, it was determined that expression of the polycystin fusion protein modulated an ATP-responsive apical chloride conductance. It is concluded that up-regulation of ATP-stimulated chloride secretion might play a significant role in cyst expansion in ADPKD.

The isolated C-terminus of polycystin-1 promotes increased ATP-stimulated chloride secretion in a collecting duct cell line.

Cyst expansion in autosomal dominant polycystic kidney disease (ADPKD) requires accumulation of fluid into the cyst lumen, which is probably driven by aberrant chloride secretion by the cyst lining epithelium. Extracellular ATP is a potent stimulus for chloride secretion in many epithelial systems, and provides a plausible mechanism for secretion in ADPKD. Therefore the link between polycystin-1 and ATP-stimulated chloride secretion was investigated in the M1 cortical collecting duct cell line. M1 cells were stably transfected with a glucocorticoid-inducible cytoplasmic C-terminal polycystin-1 construct fused to a membrane expression cassette. Induction of fusion protein expression was associated with augmentation of ATP-stimulated transepithelial chloride secretion. After nystatin-induced permeabilization of the basolateral membrane, it was determined that expression of the polycystin fusion protein modulated an ATP-responsive apical chloride conductance. It is concluded that up-regulation of ATP-stimulated chloride secretion might play a significant role in cyst expansion in ADPKD.