Abstract
Reconstitution of total nephron segments after resection in the adult kidney has not been achieved; however, whether the neonatal kidney can maintain the capacity for neo-nephrogenesis after resection is unknown. We performed partial resection of the kidney in neonatal rats on postnatal days 1 (P1x kidney) and 4 (P4x kidney) and examined morphological changes and relevant factors. The P1x kidney bulged into the newly formed cortex from the wound edge, while nephrogenesis failure was prominent in the P4x kidney. Twenty-eight days post-resection, the glomerular number, cortex area, and collecting duct were preserved in the P1x kidney, whereas these parameters were markedly decreased in the P4x kidney. During normal development, Six2 expression and Six2+ nephron progenitor cells in the cap mesenchyme both rapidly disappear after birth. However, time course analysis for the P1x kidney showed that Six2 expression and Six2+ cells were well preserved in the tissue surrounding the resected area even 2 days after resection. In conclusion, our results indicate that kidneys in early neonate rats retain the capability for neo-nephrogenesis after resection; however, this ability is lost soon after birth, which may be attributed to a declining amount of Six2+ cells.
Highlights
Regeneration is characterized as a process of renewal, restoration, and reformation of the tissue that is lost due to various insults, and it has been investigated for several hundreds of years in various species[1]
We validated the surgical procedure to ensure similar insult in both groups based on Periodic Acid-Schiff (PAS) staining of resected kidneys, which revealed that the resection reached the cortico-medullary junction in both P1x and P4x kidneys, and that the medullary tissue was exposed on the surface to some extent (Fig. 1c, Supplementary Fig. S1, 0 dpr)
The parenchymal tissues around the edge of the wound gradually started to grow towards the center of the resected surface, and the bulk of the resected tissue was re-covered with vestiges, such as a flattened surface by parenchymal tissue in the P1x kidney at 28 dpr (Fig. 1c, Supplementary Fig. S1, 28 dpr)
Summary
Regeneration is characterized as a process of renewal, restoration, and reformation of the tissue that is lost due to various insults, and it has been investigated for several hundreds of years in various species[1]. Some tissues such as the heart, lung, and kidney exhibit a much lower rate of cell turnover[6] Lineage analysis of these tissues has shown that even after injury and repair, the contribution of the stem/progenitor population, if it exists, to organ regeneration is quite small[7,8]. Lineage analysis of terminally differentiated tubular epithelial cells excluded the contribution of intratubular progenitors and endogenous progenitors to the repair process in rodents[7,22] These results indicate that the effect of cell therapy on kidney injury is not attributed to cell transdifferentiation into mature proximal tubular epithelia, but rather to paracrine systems[23,24]. Pediatric and adolescent renal disorders may be reverted to neonatal regeneration
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