Table 4.
MRTF in kidney diseases.
| Disease | Animal/Cell Model | Experimental Conditions | Suggested Mechanim | Reference |
|---|---|---|---|---|
| Diabetic nephropathy | REC cell model and WT rat |
SCAI overexpression, rat UUO | SCAI → blocks MRTF-A → locks fibrosis | [126] |
| Mrtf-a KO mice and fibroblasts | In vivo (STZ, high fat diet), in vitro (STZ, high glucose) |
MRTF-A is necessary to recruit histone acetyl- transferase and methyl- transferase to collagen promoters and activate type I collagen transcription | [123] | |
| MRTF-A KO mice and | In vivo (STZ, high fat diet) In vitro (STZ, high glucose) |
MRTF-A regulates histone acetylation and methylation on the CTGF promoter, partially through interacting with KDM3A | [90] | |
| Obstructive nephropathy | WT mice, REC cell model | UUO, in vitro functional studies | Epithelial MRTF-A links cytoskeletal and organization to redox state, through NOX4 | [153] |
| AMPK1α KO conditional (fibroblast) | UUO | AMPK1α → cofilin →F-actin → nuclear MRTF-A | [239] | |
| WT mice | UUO, MRTF-A inhibitor (CCG1423) | RhoA → MRTF-A → TAZ → PEP → fibrogenesis | [124,220,240,241] | |
| WT mice | UUO+ SCAI inhibition | SCAI → blocks MRTF-A → blocks fibrosis |
[126] | |
| Acute kidney injury | Macrophage-specific MRTF-A KO mice | Ischemia-reperfusion lipopolysaccharide |
MRTF-A → MYST1 → H4K16Ac at NOX → ROS | [154] |
| Polycystic kidney disease | PKD patients | Microarray comparison | MRTF-A/SRF transcription network is upregulated | [242] |
| PKD1 KO in tubules | Loss of PKD → LARG → RhoA → YAP/TAZ → c-Myc → cystogenesis | [243] | ||
| PKD1 patients PKD1 KO mice |
ROK-inhibitor (hydroxyfasudyl) treatment | Loss of PKD → ArhGAP35 → RhoA/ROK | [244] | |
| Pkd2+/−vascular smooth muscle | phenylephrin stimulation | Loss of PKD → RhoA → F-actin → αSMA |
[245,246] | |
| Pkd1 and Pkd2 KO mice | Expression and localization studies |
Increased MRTF expression and nuclear localization |
Kapus lab, unpublished data |