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Journal of Environmental Pathology, Toxicology and Oncology
Fator do impacto: 1.625 FI de cinco anos: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN Imprimir: 0731-8898
ISSN On-line: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.v31.i3.90
pages 285-293

Calcium Ameliorates Renal Cyst Growth in Metanephric Organ Culture: A Morphological Study

Nidhi Mahajan
Department of Biochemistry, Panjab University, Chandigarh-160014, India
Tarundeep Kaur
Department of Biochemistry, Panjab University, Chandigarh-160014, India
Veena Puri
Centre for Systems Biology & Bioinformatics, Panjab University, Chandigarh-160014, India
Surindar Singla
Panjab University
Vivekanand Jha
Department of Nephrology, PGIMER, Chandigarh-160012, India
Sanjeev Puri
Department of Biotechnology, University Institute of Engineering & Technology, Panjab University, Chandigarh, India

RESUMO

Polycystic kidney disease (PKD) is associated with alterations in developmental processes that severely affect kidney integrity, often leading to fatal consequences. It has been suggested that dysfunctional calcium (Ca2+) regulation associated with the PKD phenotype is consequent to mutations affecting the pkd1 gene. Previously, it has been observed that blocking calcium along with cAMP allowed tubular epithelial cells to enter the proliferative phase that culminated in a cyst-like phenotype. In this regard, mouse metanephroi, (embryonic day 13.5, E13.5) were used to study morphological and ultrastructural effects of calcium replenishment on 8-bromocyclic 3'5'cyclic adenosine monophosphate (8-Br-cAMP)-induced cyst-like tubular dilations. Phase contrast microscopy of 8-Br-cAMP-treated metanephroi exhibited numerous dilated tubules that continued to increase in size for 4 days in culture. The effects of 8-Br-cAMP on renal tubular epithelia were assessed by histopathological and electron microscopic analyses. Transmission electron microscopy revealed changes such as increased vacuolation, swollen mitochondria, chromatin condensation, and disrupted cell membrane in tubular epithelia of 8-Br-cAMP-treated metanephroi. Concurrent treatments with calcium-channel agonists (calcium ionophore A23187 and phorbol-12-myristate-13-acetate) and 8-Br-cAMP abolished cAMP-induced morphometric and ultrastructural alterations. Calcium replenishment rescued tubular epithelial cells from mitogenic effects of cAMP and restored normal morphology at cellular and sub-cellular levels as verified by histopathological and ultrastructural examinations.


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