scholarly journals 1992 Homer Smith Award. Fluid secretion, cellular proliferation, and the pathogenesis of renal epithelial cysts.

1993 ◽  
Vol 3 (12) ◽  
pp. 1841-1857 ◽  
Author(s):  
J J Grantham
Keyword(s):  
Growth Factors ◽  
Epithelial Cells ◽  
Cellular Proliferation ◽  
Early Stage ◽  
Renal Cysts ◽  
Fluid Secretion ◽  
Cyst Formation ◽  
Renal Tubules ◽  
Epidermal Growth

Renal cysts, caused by hereditary or acquired disorders, develop in tubule segments. The central pathogenetic elements of cyst formation include abnormal cellular proliferation, accumulation of intratubular liquid, and remodeling of the extracellular matrix. This review addresses the pathogenetic basis of liquid collection and cellular proliferation. Cavity liquid. At an early stage of growth, most renal cysts become detached from the tubule segment of origin; thus, transepithelial fluid secretion is the source of the liquid in most macroscopic cysts. Evidence from in situ and in vitro studies of intact cysts and epithelium cultured from cyst walls and normal renal tubules indicates that: (1) solutes (NaCl) are secreted into the cysts and water flows secondarily by osmosis; (2) active Na+ transport has a primary or secondary role in the secretion of Na+ and Cl-; and (3) the rate of liquid secretion can be modulated by hormones (arginine vasopressin), autocoids (prostaglandin E1 and E2), growth factors (epidermal growth factor), and unknown factors in cyst fluids. Cellular proliferation. Epithelial cells of renal cysts appear to proliferate more than normal. Each cyst resembles a tumor, except that the mass is composed primarily of liquid rather than cells. The proliferation of cyst epithelial cells is associated with: (1) abnormal expression of proto-oncogenes; (2) abnormal displays of morphologic and biochemical phenotypic markers; and (3) abnormal responsiveness to growth factors. The maturation arrest hypothesis, introduced as a framework to explore the pathogenetic basis of all renal cysts, supposes that the epithelial cells comprising cysts are "locked" in an immature, dedifferentiated state. Therapeutic strategies to control the growth of renal cysts may reasonably target processes that inhibit fluid secretion, maximize fluid absorption, and redifferentiate the immature and abnormally proliferative epithelial cells within cysts.

scholarly journals Cyst fluid from human autosomal dominant polycystic kidneys promotes cyst formation and expansion by renal epithelial cells in vitro.

1992 ◽  
Vol 3 (4) ◽  
pp. 984-994
Author(s):  
M Ye ◽  
M Grant ◽  
M Sharma ◽  
L Elzinga ◽  
S Swan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Autosomal Dominant ◽  
Renal Cysts ◽  
Secretory Activity ◽  
Collagen Matrix ◽  
Fluid Secretion ◽  
Cyst Formation ◽  
Cyst Fluid ◽  
Epidermal Growth

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive renal enlargement, culminating in renal insufficiency in over one half of affected individuals. The highly variable onset and clinical course of ADPKD may be due to factors extrinsic to the genetically defined renal cysts. In this study, cyst fluid samples from 12 nonazotemic and 18 azotemic ADPKD subjects were examined for in vitro biologic activity that promotes cellular proliferation and the secretion of fluid by renal epithelial monolayers, two pathogenetic mechanisms that have critical roles in the formation and the rate of expansion of renal cysts. Cyst fluid added to culture medium (final concentrations, 1 to 20%) caused Madin-Darby canine kidney cells and human kidney cortex (HKC) cells derived from primary cultures to form cysts in Type I collagen matrix. Cyst fluid stimulated the net transepithelial secretion of fluid by polarized monolayers composed of these same cells. Absolute levels of fluid secretory activity determined by MDCK bioassay were correlated directly with the rate of fluid secretion by HKC cell monolayers and with the extent of cyst formation by MDCK and HKC cells embedded in collagen matrix. The secretory activity of urine was negligible; secretory activity was detectable in the serum of normal and ADPKD subjects, but the levels were much lower than in cyst fluid. cAMP agonists prostaglandins E1 and E2, arginine vasopressin, and 8-Br-cAMP stimulated fluid secretion by MDCK and HKC monolayers, but these substances did not cause HKC cells to form cysts in collagen matrix, whereas cyst fluid did. Among other naturally occurring growth factors and autacoids, only epidermal growth factor and transforming growth factor alpha stimulated cyst formation by HKC cells; however, the capacity of cyst fluid to stimulate fluid secretion was not affected by treatment with antiserum to epidermal growth factor. It was concluded that potent, and possibly unique, substances in the cyst fluids of individuals with ADPKD support and augment biologic processes in renal epithelial cells that may be important in the promotion of progressive cyst expansion.

cAMP-dependent chloride secretion mediates tubule enlargement and cyst formation by cultured mammalian collecting duct cells

2009 ◽  
Vol 296 (2) ◽  
pp. F446-F457 ◽  
Author(s):  
Roberto Montesano ◽  
Hafida Ghzili ◽  
Fabio Carrozzino ◽  
Bernard C. Rossier ◽  
Eric Féraille
Keyword(s):  
Molecular Mechanisms ◽  
Kidney Diseases ◽  
Collecting Duct ◽  
Fluid Secretion ◽  
Cyst Formation ◽  
Chloride Secretion ◽  
Cystic Kidney ◽  
Pcr Analysis ◽  
Renal Tubules

Polycystic kidney diseases result from disruption of the genetically defined program that controls the size and geometry of renal tubules. Cysts which frequently arise from the collecting duct (CD) result from cell proliferation and fluid secretion. From mCCDcl1 cells, a differentiated mouse CD cell line, we isolated a clonal subpopulation (mCCD-N21) that retains morphogenetic capacity. When grown in three-dimensional gels, mCCD-N21 cells formed highly organized tubular structures consisting of a palisade of polarized epithelial cells surrounding a cylindrical lumen. Subsequent addition of cAMP-elevating agents (forskolin or cholera toxin) or of membrane-permeable cAMP analogs (CPT-cAMP) resulted in rapid and progressive dilatation of existing tubules, leading to the formation of cystlike structures. When grown on filters, mCCD-N21 cells exhibited a high transepithelial resistance as well as aldosterone- and/or vasopressin-induced amiloride-sensitive and -insensitive current. The latter was in part inhibited by Na+-K+-2Cl− cotransporter (bumetanide) and chloride channel (NPPB) inhibitors. Real-time PCR analysis confirmed the expression of NKCC1, the ubiquitous Na+-K+-2Cl− cotransporter and cystic fibrosis transmembrane regulator (CFTR) in mCCD-N21 cells. Tubule enlargement and cyst formation were prevented by inhibitors of Na+-K+-2Cl− cotransporters (bumetanide or ethacrynic acid) or CFTR (NPPB or CFTR inhibitor-172). These results further support the notion that cAMP signaling plays a key role in renal cyst formation, at least in part by promoting chloride-driven fluid secretion. This new in vitro model of tubule-to-cyst conversion affords a unique opportunity for investigating the molecular mechanisms that govern the architecture of epithelial tubes, as well as for dissecting the pathophysiological processes underlying cystic kidney diseases.

Mitogenic actions of endothelin and other growth factors in ovine endometrium

1997 ◽  
Vol 152 (2) ◽  
pp. 283-290 ◽  
Author(s):  
L A Salamonsen ◽  
R J Young ◽  
S Garcia ◽  
J K Findlay
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Stromal Cells ◽  
Cellular Proliferation ◽  
Calf Serum ◽  
Dose Dependence ◽  
Leukaemia Inhibitory Factor ◽  
Serum Free

Abstract Endothelin-1 (ET-1) is present in ovine endometrium, primarily in epithelial cells, and increases around the time of implantation. We examined the cell type expressing ET-binding sites in vitro and whether ET-1 has mitogenic actions in the endometrium, alone or in synergy with other growth factors. Purified epithelial and stromal cells were prepared from luteal-phase endometrium. Specific receptors were demonstrated by binding of 125I-ET-1 and proliferative effects of ET-1 and/or other growth factors determined by uptake of [3H]thymidine by cells in serum-free culture. 125I-ET-1 bound to both epithelial (2516 ± 820 c.p.m./well) and stromal (6368 ± 1350 c.p.m./well) cells and was displaced by ET-1 (1 μmol l−1). There were no proliferative effects of ET on epithelial cells. ET-1 (10 nmol l−1) stimulated uptake of [3H]thymidine by stromal cells under serum-free conditions in 13/20 individual cell preparations, to 149 ± 13% of control (untreated=100%) with dose-dependence between the range of 1 to 100 nmol l−1. Stimulation by fetal calf serum was to 377 ± 126% of control. The effects on proliferation by other growth factors (dose; % of control ± s.e.m., number of positives/total number of cell preparations) were: IGF-I (13 nmol l−1; 182 ± 14, 4/4), epidermal growth factor (EGF; 4·8 nmol l−1; 132 ± 5%, 7/7), platelet-derived growth factor-BB (0·4 nmol l−1; 146 ± 3, 2/2) and leukaemia inhibitory factor (0·4 nmol l−1; 110 ± 2, 3/3). All stimulations except that of EGF were significant and dose-responsive but only insulin was additive with ET (350 ± 35, 5/5). ET-1 also stimulated expression of the the AP-1 cis element c-jun, this being maximal at 60 min of exposure to mitogen. ET-1, along with other growth factors has a likely paracrine role in cellular proliferation in the endometrium, possibly in association with blastocyst implantation. Journal of Endocrinology (1997) 152, 283–290

scholarly journals Berberine and Obatoclax Inhibit SARS-Cov-2 Replication in Primary Human Nasal Epithelial Cells In Vitro

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 282
Author(s):  
Finny S. Varghese ◽  
Esther van Woudenbergh ◽  
Gijs J. Overheul ◽  
Marc J. Eleveld ◽  
Lisa Kurver ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Early Stage ◽  
Antiviral Drugs ◽  
Target Cells ◽  
Nasal Epithelial Cells ◽  
Cytokines And Chemokines ◽  
Human Nasal Epithelial Cells ◽  
Apoptotic Protein ◽  
Air Liquid Interface

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a new human pathogen in late 2019 and it has infected over 100 million people in less than a year. There is a clear need for effective antiviral drugs to complement current preventive measures, including vaccines. In this study, we demonstrate that berberine and obatoclax, two broad-spectrum antiviral compounds, are effective against multiple isolates of SARS-CoV-2. Berberine, a plant-derived alkaloid, inhibited SARS-CoV-2 at low micromolar concentrations and obatoclax, which was originally developed as an anti-apoptotic protein antagonist, was effective at sub-micromolar concentrations. Time-of-addition studies indicated that berberine acts on the late stage of the viral life cycle. In agreement, berberine mildly affected viral RNA synthesis, but it strongly reduced infectious viral titers, leading to an increase in the particle-to-pfu ratio. In contrast, obatoclax acted at the early stage of the infection, which is in line with its activity to neutralize the acidic environment in endosomes. We assessed infection of primary human nasal epithelial cells that were cultured on an air-liquid interface and found that SARS-CoV-2 infection induced and repressed expression of specific sets of cytokines and chemokines. Moreover, both obatoclax and berberine inhibited SARS-CoV-2 replication in these primary target cells. We propose berberine and obatoclax as potential antiviral drugs against SARS-CoV-2 that could be considered for further efficacy testing.

scholarly journals Efficient functional cyst formation of biliary epithelial cells using microwells for potential bile duct organisation in vitro

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Astia Rizki-Safitri ◽  
Marie Shinohara ◽  
Yasushi Miura ◽  
Mathieu Danoy ◽  
Minoru Tanaka ◽  
...  
Keyword(s):  
Bile Duct ◽  
Epithelial Cells ◽  
Cyst Formation ◽  
Biliary Epithelial Cells

scholarly journals A Comparative Transcriptome Analysis of Human and Porcine Choroid Plexus Cells in Response to Streptococcus suis Serotype 2 Infection Points to a Role of Hypoxia

2021 ◽  
Vol 11 ◽  
Author(s):  
Alexa N. Lauer ◽  
Rene Scholtysik ◽  
Andreas Beineke ◽  
Christoph Georg Baums ◽  
Kristin Klose ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Response ◽  
Choroid Plexus ◽  
Cellular Proliferation ◽  
Inflammatory Responses ◽  
Streptococcus Suis ◽  
Gene Set Enrichment Analysis ◽  
Rna Seq

Streptococcus suis (S. suis) is an important opportunistic pathogen, which can cause septicemia and meningitis in pigs and humans. Previous in vivo observations in S. suis-infected pigs revealed lesions at the choroid plexus (CP). In vitro experiments with primary porcine CP epithelial cells (PCPEC) and human CP epithelial papilloma (HIBCPP) cells demonstrated that S. suis can invade and traverse the CP epithelium, and that the CP contributes to the inflammatory response via cytokine expression. Here, next generation sequencing (RNA-seq) was used to compare global transcriptome profiles of PCPEC and HIBCPP cells challenged with S. suis serotype (ST) 2 infected in vitro, and of pigs infected in vivo. Identified differentially expressed genes (DEGs) were, amongst others, involved in inflammatory responses and hypoxia. The RNA-seq data were validated via quantitative PCR of selected DEGs. Employing Gene Set Enrichment Analysis (GSEA), 18, 28, and 21 enriched hallmark gene sets (GSs) were identified for infected HIBCPP cells, PCPEC, and in the CP of pigs suffering from S. suis ST2 meningitis, respectively, of which eight GSs overlapped between the three different sample sets. The majority of these GSs are involved in cellular signaling and pathways, immune response, and development, including inflammatory response and hypoxia. In contrast, suppressed GSs observed during in vitro and in vivo S. suis ST2 infections included those, which were involved in cellular proliferation and metabolic processes. This study suggests that similar cellular processes occur in infected human and porcine CP epithelial cells, especially in terms of inflammatory response.

Embryo co-culture with bovine amniotic membrane stem cells can enhance the cryo-survival of IVF-derived bovine blastocysts comparable with co-culture with bovine oviduct epithelial cells

Zygote ◽  
2020 ◽  
pp. 1-6
Author(s):  
Shayan Nejat-Dehkordi ◽  
Ebrahim Ahmadi ◽  
Abolfazl Shirazi ◽  
Hassan Nazari ◽  
Naser Shams-Esfandabadi
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Epithelial Cells ◽  
Embryonic Development ◽  
Amniotic Membrane ◽  
Biological Activities ◽  
Survival Rates ◽  
Blastocyst Stage ◽  
Oviduct Epithelial Cells

Summary Culture conditions have a profound effect on the quality of in vitro-produced embryos. Co-culturing embryos with somatic cells has some beneficial effects on embryonic development. Considering the ability of stem cells to secrete a broad range of growth factors with different biological activities, we hypothesized that bovine amniotic membrane stem cells (bAMSCs) might be superior to bovine oviduct epithelial cells (BOECs) in supporting embryonic development and enhancing their cryo-survival. Bovine abattoir-derived oocytes were matured and fertilized in vitro. The resultant presumptive zygotes were then cultured up to the blastocyst stage in the following groups: (i) co-culture with bAMSCs, (ii) co-culture with BOECs, and (iii) cell-free culture (Con). Embryos that reached the blastocyst stage were vitrified and warmed, and their post-warming re-expansion, survival and hatching rates were evaluated after 72 h culture. Results showed that the cleavage, blastocyst, and 2 h post-warming re-expansion rates of embryos did not differ between groups. However, their survival rates in BOEC and bAMSC groups were significantly higher compared with the control (72.7, 75.6 and 37.5%, respectively, P < 0.05). In conclusion, our results showed that the cryo-survivability of IVF-derived bovine embryos could be improved through co-culturing with bAMSCs. Moreover, considering the possibility to provide multiple passages from bAMSCs compared with BOECs, due to their stemness properties and their ability to produce growth factors, the use of bAMSCs is a good alternative to BOECs in embryo co-culture systems.

Secretory NaCl and volume flow in renal tubules

1986 ◽  
Vol 250 (5) ◽  
pp. R753-R763 ◽  
Author(s):  
K. W. Beyenbach
Keyword(s):  
Fluid Secretion ◽  
Renal Tissue ◽  
Tubular Secretion ◽  
Proximal Tubules ◽  
Epithelial Cell Line ◽  
Renal Tubules ◽  
Genetic Potential ◽  
Dog Kidney ◽  
Nacl Secretion

This review attempts to give a retrospective survey of the available evidence concerning the secretion of NaCl and fluid in renal tubules of the vertebrate kidney. In the absence of glomerular filtration, epithelial secretory mechanisms, which to this date have not been elucidated, are responsible for the renal excretion of NaCl and water in aglomerular fish. However, proximal tubules isolated from glomerular fish kidneys of the flounder, killifish, and the shark also have the capacity to secrete NaCl and fluid. In shark proximal tubules, fluid secretion appears to be driven via secondary active transport of Cl. In another marine vertebrate, the sea snake, secretion of Na (presumably NaCl) and fluid is observed in freshwater-adapted and water-loaded animals. Proximal tubules of mammals can be made to secrete NaCl in vitro together with secretion of aryl acids. An epithelial cell line derived from dog kidney exhibits secondary active secretion of Cl when stimulated with catecholamines. Tubular secretion of NaCl and fluid may serve a variety of renal functions, all of which are considered here. The occurrence of NaCl and fluid secretion in glomerular proximal tubules of teleosts, elasmobranchs, and reptiles and in mammalian renal tissue cultures suggests that the genetic potential for NaCl secretion is present in every vertebrate kidney.

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