Abstract
Background
The expression in the glomerular mesangial cells, papillary, and collecting duct cells demonstrated annexin A1 (AnxA1)’s role in specific renal functions. With varying concentrations of calcium (Ca2+), it is considered to regulate cellular processes such as cell proliferation, apoptosis, and clearance of apoptotic cells by forming ceramides, a key lipid mediator of apoptosis. It also participates in tumorigenesis based on its location. On account of these features, we investigated the expression of this apoptosis-associated protein in fetal kidneys at different gestational periods, mature kidneys and in kidney cancer tissues in order to localize and possibly characterize its role during nephrogenesis and renal tumors.
Methods
AnxA1 expression was evaluated by an immunohistochemistry technique in “paraffin-embedded” renal tissue sections from autopsied fetuses at different gestational ages, in mature kidneys and renal cancer tissues.
Results
The current study data demonstrated that AnxA1 is expressed in the mesangial cells and podocytes of maturing glomeruli in the developing renal cortex of fetal kidneys at 14 to 19 weeks of gestation. The expression in the mesangial cells declined in later weeks of gestation and persisted into adulthood. AnxA1 expression increased with the progression of clear cell renal cell carcinoma (CCRCC) and also in other cancer types indicating a potential role of the protein in tumorigenesis.
Conclusions
We presume that AnxA1 in the podocytes and mesangial cells play important roles in various signaling pathways in the functioning of the glomerulus. These results and concepts provide a framework to further dissect its biological properties and thereby develop diagnostic, prognostic, and therapeutic strategies targeting the molecule in various renal pathologies.
Acknowledgments
The authors would like to acknowledge the help of Mr. Clinton D’ Souza and Mr. ShashidharAngadi for technical assistance.
Author contributions: Conceived the idea and designed the experiments: RS and PKS; helped in clinical sample collection and correlated the clinical relevance to the study: USD, BMB and SKD; Performed the experiments: RS, SE, AB, and KR; analyzed the data (pathology): USD. Analyzed the data (statistical analysis): RS, PKS, JKV, and AB; manuscript preparation: RS and PKS; revised the manuscript: PKS and JKV; supervised the overall study: PKS and BMB.
Research funding: None declared.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: Research involving human subjects compliedwith all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013), and has been approved by the authors’ Institutional Review Board or equivalent committee.
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