Pharmacological inhibition of MyD88 suppresses inflammation in tubular epithelial cells and prevents diabetic nephropathy in experimental mice.

ABSTRACT: Emerging evidence shows that chronic inflammation mediated by toll-like receptors (TLRs) contributes to diabetic nephropathy. Myeloid differentiation primary-response protein-88 (MyD88) is an essential adapter protein of all TLRs except TLR3 in innate immunity. It is unclear whether MyD88 could be a therapeutic target for diabetic nephropathy. Here, we used a new small-molecule MyD88 inhibitor, LM8, to examine the pharmacological inhibition of MyD88 in protecting kidneys from inflammatory injury in diabetes. We showed that MyD88 was significantly activated in the kidney of STZ-induced type 1 diabetic mice in tubular epithelial cells as well as in high glucose-treated rat tubular epithelial cells NRK-52E. In cultured tubular epithelial cells, we show that LM8 (2.5-10 μM) or MyD88 siRNA atte

SUBMITTER: Zhang QY 

PROVIDER: S-EPMC8792016 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature