Abstract
Kidney hypertrophy is a common clinical feature in patients with diabetes and is associated with poor renal outcomes. Initial cell proliferation followed by cellular hypertrophy are considered the responsible mechanisms for diabetic kidney hypertrophy. However, whether similar responses against hyperglycemia continue in the chronic phase in diabetes is unclear. We performed lineage tracing analysis of proximal tubular epithelia using novel type 2 diabetic mice with a tamoxifen-inducible proximal tubule-specific fluorescent reporter. Clonal analysis of proximal tubular epithelia demonstrated that the labeled epithelia proliferated in type 2 diabetic mice. Based on the histological analysis and protein/DNA ratio of sorted labeled tubular epithelia, there was no evidence of cellular hypertrophy in type 2 diabetic mice. Lineage tracing and histological analyses of streptozocin-induced type 1 diabetes also revealed that cellular proliferation occurs in the chronic phase of type 1 diabetes induction. According to our study, epithelial proliferation accompanied by SGLT2 upregulation, rather than cellular hypertrophy, predominantly occurs in the hypertrophic kidney in both type 1 and type 2 diabetes. An increased number of SGLT2+ tubular epithelia may be an adaptive response against hyperglycemia, and linked to the hyper-reabsorption of sodium and glucose observed in type 2 diabetes patients.
Highlights
For evaluating or visualizing cell division, especially in acute kidney injury, immunostaining of markers or labeling of proliferating cells by thymidine analogs are common experimental methods
This study addressed the cellular responses of proximal tubular epithelial cells in the early diabetic kidney using lineage tracing analysis of terminally differentiated proximal tubular epithelia
Our clonal analysis of proximal tubular epithelia labeled at the single-cell level demonstrated active cell proliferation in the kidney in both type 1 and type 2 diabetic mouse models
Summary
For evaluating or visualizing cell division, especially in acute kidney injury, immunostaining of markers or labeling of proliferating cells by thymidine analogs are common experimental methods. These strategies are not sufficient for clearly demonstrating cell division in cells with a slower turnover, which is a major problem for visualizing the effects of cell proliferation on kidney growth in type 2 diabetes. In order to overcome these limitations and to directly address the roles of cellular proliferation and hypertrophy in the diabetic kidney in vivo, we performed lineage tracing analysis of terminally differentiated proximal tubular epithelia. We examined the molecular changes in sorted tubular epithelia in diabetic mice by flow cytometry
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
