Loss of Hsp70 leads to increased albuminuria in a STZ-induced diabetic mouse model

Background The stress-inducible heat shock protein 70 (Hspa1a/Hspa1b) is involved in refolding of misfolded proteins as well as disaggregation of protein aggregates. Posttranslational modifications, for example by glycation during hyperglycemia, can lead to misfolding, aggregation and loss-of-function of the protein.The aim of this study was to investigate the loss of Hspa1a/Hspa1b in a STZ-induced diabetic mouse model in terms of the development of diabetic nephropathy. Methods: Diabetes was induced at the age of 10 weeks; mice were sacrificed at the age of 28 weeks. Urine was collected for 24hrs just before organ collection; albumine and creatinine were measured via ELISA. Protein expression was analyzed via Western Blot and Immunohistochemistry. Morphologic changes of diabetic nephropathy were assessed by Immunohistochemistry and electron microscopy. Results: Hspa1a/Hspa1b knockout mice (KO) did not differ from wild-type mice (WT) in the control or STZ-treated group in respect to bodyweight or blood glucose levels. STZ-treated KO mice (KO+STZ) revealed to have a significantly higher albumine/creatinine ratio (ACR) compared to STZ-treated wild-type mice (WT+STZ) and to controls (KO-STZ). KO+STZ and WT+STZ showed atrophic proximal tubuli in the outer layers of the kidney parenchyma with thickening of the basal membrane. Furthermore, WT+STZ mice showed decreased Hspa1a/Hsapa1b protein expression compared to WT-STZ mice. Conclusion: Loss of Hspa1a/Hspa1b resulted in elevated ACR in a STZ-induced diabetic mouse model. KO+STZ and WT+STZ mice, showed atrophic proximal tubuli. Furthermore, Hspa1a/Hspa1b seemed downregulated in WT+STZ mice. This supports preliminary human data, where Hspa1a/Hspa1b expression is lost in the course of diabetic nephropathy.

Interessenskonflikt

This project is funded by the German Research Foundation (DFG, SFB1118)

Publication History

Article published online:
19 August 2021