Zhen Su
Wenzhou Medical University, China
Title: Muscle-derived exosome/miR-29 attenuates kidney fibrosis in UUO mice
Biography
Biography: Zhen Su
Abstract
We hypothesized that intramuscular injection of exosome encapsulated miR-29 would counteract unilateral ureteral obstruction (UUO)-induced muscle wasting and renal fibrosis via exosome-mediated muscle-kidney crosstalk. Exosomes containing miR-29 (Exo/miR29) were prepared from the satellite cells and injected into the tibialis anterior muscle of UUO mice for one to four weeks. The expression of miR-29 was decreased in skeletal muscle and kidney of UUO mice. Serum from UUO mice enhanced secretion of exosome-encapsulated miR-29 from cultured C2C12 skeletal muscle and HEK293 renal cells. The intervention of Exo/miR29 increased muscle cross-section area and decreased UUO-induced upregulation of TRIM63/MuRF1 and FBXO32/atrogin-1. Curiously, BUN was decreased in the mice treated with Exo/miR29. In addition, renal fibrosis was partially depressed in the UUO mice with intramuscular injection of Exo/miR29. This was confirmed by decreased TGFβ, alpha-smooth muscle actin (aSMA), fibronectin, collagen 1A1 and 4A1 in the kidney of UUO mice by muscle-derived miR-29. When we used fluorescence-labeled Exo/miR-29 to trace the Exo/miR route in-vivo we found that fluorescence was significantly visible in both injected and un-injected muscle and in kidneys. The fluorescence intensity in kidney correlated with skeletal muscle. We found that miR-29 directly inhibits TGF-β3 in cultured kidney cells. We conclude that exosomes play a critical role in muscle-kidney crosstalk. Muscle-derived Exo/miR29 not only ameliorates skeletal metabolism, but also attenuates UUO-induced kidney fibrosis by down-regulating TGF-β pathway proteins and extracellular matrix components.