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JGA OF DEVELOPING, HEALTHY AND NEPHROTIC HUMAN KIDNEYS CO -EXPRESS RENIN AND CONNEXINS

Introduction: During early kidney development, renin progenitors appear within renal arteries and then gradually shift to juxtaglomerular apparatus (JGA) exclusively. JGA is a part of renin- angiotensin system (RAS) of blood pressure control and accommodates several different cell types, connected by intercellular communication proteins connexins (Cxs). Alterations in normal Cx expression are associated with vascular abnormalities and chronic kidney disease. Results of experimental studies are controversial, while studies on human kidneys are extremely rare. The aim of the present study was to describe changes in spatiotemporal expression of Cxs and renin within developing, postnatal and nephrotic human kidneys. Materials & methods: Human kidney tissue from 10 human conceptuses 8th to 38th weeks old, postnatal healthy and nephrotic kidneys was analyzed by electron microscopy and double immunofluorescence techniques, to detect localization and co- expression of Cx37, Cx40, Cx43 and Cx45 and renin in JGA. Results: Throughout development, renin was strongly expressed in the vasculature of JGA, collecting and distal tubules, and glomeruli. Similar expression pattern characterized postnatal healthy and nephrotic kidneys. JGA was characterized by strongest expression of Cx43, moderate expression of Cx40 and weak expression of Cx45 and Cx37. Cx45 was strongest in proximal tubules and Cx40 in distal tubules. Compared to healthy kidneys, nephrotic kidneys showed irregular and increased expression of Cx43 and decreased expression of Cx37 in JGA. Different levels of co-expression between renin and Cx40, Cx43, Cx45 and Cx37 characterized afferent arteriole of JGA. Conclusions: Wide distribution of renin progenitors in developing human kidneys indicate their various developmental roles, while their gradual restriction to JGA area imply their role in proper kidney vasculature development and blood pressure control. Nephrotic kidneys compared to developing and healthy postnatal kidneys showed differences in spatio-temporal patterning of Cxs and renin in JGA, pointing to proper cell communications as pre-requisite for blood pressure control.

kidney development ; renin ; connexins ; nephrotic syndrome ; blood pressure

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