MKP5 deficiency protects against pressure overload-induced cardiac hypertrophy and fibrosis

Cardiac pressure overload resulting from transaortic constriction (TAC) induces MKP-5 expression and facilitates cardiac hypertrophy and fibrosis. In this dataset, we show that MKP-5 deficiency attenuates cardiac fibrosis after TAC. In vitro, bone marrow-derived macrophages (BMDMs) from MKP-5 knockout mice exhibit enhanced phosphorylation of p38 MAPK, JNK, and Erk compared to BMDMs from wild-type mice in response to IL-4 stimulation. 

Methods
Wild-type and MKP-5 knockout mice were subjected to TAC surgery. Cardiac function was subsequently analyzed by Echo cardiography with a VisualSonics Vevo 2100 machine. Fixed mouse hearts were processed for paraffin sections and Masson's trichrome staining to visualize fibrosis. Fibrosis was quantified using Image J software. 

Bone marrow-derived macrophages from wild type and MKP-5 knockout mice were stimulated with IL-4 in culture for 0, 15, 30, 60, and 90 min and then lysed in RIPA buffer to collect protein for Western blots. Protein was separated by 10-15% SDS-PAGE and blotted for p38 MAPK total and p38 MAPK phosphorylated at Thr180/Tyr182, JNK total and JNK phosphorylated at Thr183/Tyr185,  Erk total and Erk phosphorylated at Thr202/Tyr204. Immunoblots were developed using ODYSSEY infrared Imaging SYstem (LI-COR) and quantified with Image Studio software (LI-COR version 5.2).