Cyst formation in proximal renal tubules caused by dysfunction of the microtubule minus-end regulator CAMSAP3

AbstractEpithelial cells organize an ordered array of non-centrosomal microtubules, the minus ends of which are regulated by CAMSAP3. The role of these microtubules in epithelial functions, however, is poorly understood. Here, we show that the kidneys of mice in which Camsap3 is mutated develop cysts at the proximal convoluted tubules (PCTs). PCTs were severely dilated in the mutant kidneys, and they also exhibited enhanced cell proliferation. In these PCTs, epithelial cells became flattened along with perturbation of microtubule arrays as well as of certain subcellular structures such as interdigitating basal processes. Furthermore, YAP and PIEZO1, which are known as mechanosensitive regulators for cell shaping and proliferation, were activated in these mutant PCT cells. These observations suggest that CAMSAP3-mediated microtubule networks are important for maintaining the proper mechanical properties of PCT cells, and its loss triggers cell deformation and proliferation via activation of mechanosensors, resulting in the dilation of PCTs.

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Evaluation of the Role of Na+/ K+ ATPase Ion Transporters and Na+/K+/ 2Cl and Na+/H+ Exchanger Cotransporters in Nephrons of Periophthalmus Waltoni Using Immunohistochemistry and Histology

10.21203/rs.3.rs-1046040/v1 ◽

2021 ◽

Author(s):

Kave Esfandiari ◽

Mohammad Babaei ◽

Mina Amiri-Farahani ◽

Ali Kalantari-Hesari ◽

Hassan Morovvati

Keyword(s):

Epithelial Cells ◽

Kidney Tissue ◽

Proximal Tubules ◽

Renal Tubules ◽

Ion Regulation ◽

Renal Histology ◽

Collecting Ducts ◽

Distal Tubules ◽

Periophthalmus Waltoni

Abstract Kidneys play an important role in regulating the balance of water and ions in freshwater and seawater fish. However, complex kidney structures impair a comprehensive understanding of kidney function. In this study, in addition to renal histology, Na+/K+/ATPase ion transporter proteins and Na+/K+/2Cl− and NHE3 cotransporters were located in Priophthalmus waltoni kidney tissue to evaluate the ion regulation abilities of epithelial cells in various parts of nephrons. The renal tubules are composed of proximal tubules and distal tubules, followed by collecting tubes and finally collecting ducts. Light microscope immunohistochemistry was utilized to locate Na+/ K+-ATPase along renal tubules and collecting ducts. However, the distribution of the Na+/K+-ATPase immune response varies in different sections. Na+/K+/CL− cotransporter positioning was reported only in collecting tubes and collecting ducts, and proximal tubes and distal tubes did not respond to Na+/K+/Cl− cotransporter immunolocalization. Immunohistochemical response for NHE3 localization was detected only at the apex of epithelial cells of proximal tubules and collecting tubes. The distal tubes showed negative reaction and the collecting ducts showed a weak response to NHE3 safety immunolocalization.

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The rôle of immunological reactions in apical cyst formation and the fate of epithelial cells after root canal therapy: a theory

International Journal of Oral Surgery ◽

10.1016/s0300-9785(83)80075-1 ◽

1983 ◽

Vol 12 (1) ◽

pp. 14-22 ◽

Cited By ~ 21

Author(s):

Mahmoud Torabinejad

Keyword(s):

Epithelial Cells ◽

Root Canal ◽

Cyst Formation ◽

Root Canal Therapy ◽

Immunological Reactions

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EP2 receptor mediates PGE2-induced cystogenesis of human renal epithelial cells

AJP Renal Physiology ◽

10.1152/ajprenal.00036.2007 ◽

2007 ◽

Vol 293 (5) ◽

pp. F1622-F1632 ◽

Cited By ~ 31

Author(s):

Gerard Elberg ◽

Dorit Elberg ◽

Teresa V. Lewis ◽

Suresh Guruswamy ◽

Lijuan Chen ◽

...

Keyword(s):

Kidney Disease ◽

Epithelial Cells ◽

Polycystic Kidney Disease ◽

Cyst Formation ◽

Cyst Fluid ◽

Receptor Expression ◽

Camp Signaling ◽

Polycystic Kidney ◽

Camp Formation

Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by formation of cysts from tubular epithelial cells. Previous studies indicate that secretion of prostaglandin E2 (PGE2) into cyst fluid and production of cAMP underlie cyst expansion. However, the mechanism by which PGE2 directly stimulates cAMP formation and modulates cystogenesis is still unclear, because the particular E-prostanoid (EP) receptor mediating the PGE2 effect has not been characterized. Our goal is to define the PGE2 receptor subtype involved in ADPKD. We used a three-dimensional cell-culture system of human epithelial cells from normal and ADPKD kidneys in primary cultures to demonstrate that PGE2 induces cyst formation. Biochemical evidence gathered by using real-time RT-PCR mRNA analysis and immunodetection indicate the presence of EP2 receptor in cystic epithelial cells in ADPKD kidney. Pharmacological evidence obtained by using PGE2-selective analogs further demonstrates that EP2 mediates cAMP formation and cystogenesis. Functional evidence for a role of EP2 receptor in mediating cAMP signaling was also provided by inhibiting EP2 receptor expression with transfection of small interfering RNA in cystic epithelial cells. Our results indicate that PGE2 produced in cyst fluid binds to adjacent EP2 receptors located on the apical side of cysts and stimulates EP2 receptor expression. PGE2 binding to EP2 receptor leads to cAMP signaling and cystogenesis by a mechanism that involves protection of cystic epithelial cells from apoptosis. The role of EP2 receptor in mediating the PGE2 effect on stimulating cyst formation may have direct pharmacological implications for the treatment of polycystic kidney disease.

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

Journal of the American Society of Nephrology ◽

10.1681/asn.v3121841 ◽

1993 ◽

Vol 3 (12) ◽

pp. 1841-1857 ◽

Cited By ~ 1

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.

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Effect of Calcium on the Growth and Differentiation of Cultured Rat Esophageal Epithelial Cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053383 ◽

1982 ◽

Vol 40 ◽

pp. 132-133

Author(s):

W.T. Gunning ◽

M.R. Marino ◽

M.S. Babcock ◽

G.D. Stoner

Keyword(s):

Epithelial Cells ◽

Cell Types ◽

Replication Rate ◽

Enzymatic Dissociation ◽

Growth Assay ◽

Epidermal Growth ◽

Fetal Bovine ◽

Esophageal Epithelial Cells ◽

Cellular Replication

The role of calcium in modulating cellular replication and differentiation has been described for various cell types. In the present study, the effects of Ca++ on the growth and differentiation of cultured rat esophageal epithelial cells was investigated.Epithelial cells were isolated from esophagi taken from 8 week-old male CDF rats by the enzymatic dissociation method of Kaighn. The cells were cultured in PFMR-4 medium supplemented with 0.25 mg/ml dialyzed fetal bovine serum, 5 ng/ml epidermal growth factor, 10-6 M hydrocortisone 10-6 M phosphoethanolamine, 10-6 M ethanolamine, 5 pg/ml insulin, 5 ng/ml transferrin, 10 ng/ml cholera toxin and 50 ng/ml garamycin at 36.5°C in a humidified atmosphere of 3% CO2 in air. At weekly intervals, the cells were subcultured with a solution containing 1% polyvinylpyrrolidone, 0.01% EGTA, and 0.05% trypsin. After various passages, the replication rate of the cells in PFMR-4 medium containing from 10-6 M to 10-3 M Ca++ was determined using a clonal growth assay.

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