miR-129-5p alleviates LPS-induced acute kidney injury via targeting HMGB1/TLRs/NF-kappaB pathway

Xin Huang, Xiangping Hou, Libo Chuan, Shutao Wei, Jingrong Wang, Xiaohua Yang, Jin Ru
International Immunopharmacology 2020 October 8, 89 (Pt A): 107016

INTRODUCTION: The present study aimed to investigate whether miR-129-5p can regulate high-mobility group box protein 1 (HMGB1)-modulated TLRs/NF-kappaB inflammatory pathway that contributed to lipopolysaccharide (LPS)-induced podocyte apoptosis and acutekidneyinjury (AKI).

MATERIAL AND METHODS: In vitro and in vivo models of sepsis were simulated using LPS-administrated podocytes and mice, respectively. The effects of LPS, mR-129-5p mimics and short hairpin RNA of HMGB1 (sh-HMGB1) on podocyte apoptosis were monitored using TUNEL staining. Protein expression was measured using western blotting. Survival outcomes were analyzed in septic mice with agomir-mR-129-5p administration.

RESULTS: We observed that stimulation of podocytes with LPS significantly inhibits the expression of miR-129-5p, and overexpression of miR-129-5p protects against LPS-induced podocyte damage, over-activation of inflammatory response and apoptosis. In a mouse model, agomir-miR-129-5p administration significantly improves the survival outcomes in septic mice and LPS-induced AKI. Mechanically, LPS-induced the elevation of HMGB1, TLR2, TLR4 and nuclear NF-κB protein expression in vitro and in vivo are restrained by the overexpression of miR-129-5p.

CONCLUSIONS: Overexpression of miR-129-5p protects against LPS-induced podocyte apoptosis, inflammation and AKI in vivo and in vitro models of sepsis. The underlying molecular mechanism is mediated via attenuating HMGB1/TLRs/NF-κB signaling axis modulated inflammatory response.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"