Table 3.

Regulatory Mechanism of Nox4 in Diabetic cardiomyopathy.

Models	Intervention	Regulating factors/Signal pathways	Main results	Conclusion	Reference
The myocardial tissue of STZ-induced diabetic rat	–	Nox4-ROS-ERK	Collagen Ⅰ/Ⅲ↑, MMP-2/9↑, Nox4↑, Phosphorylated ERK1/2↑, ROS↑	Nox4 plays an important role in the fibrotic process of diabetic cardiomyopathy and may be an important target for the prevention and treatment of diabetic cardiomyopathy.	[110]
The myocardial tissue of STZ-induced diabetic rat	Ang II receptor blockers	Ang II/Nox4	AT1R↓, Nox4↓, p22phox↓, Oxidative stress↓, TGF-β↓, improved cardiac function	The regulation of Nox4 by Ang II or TGF-β may play a critical role in the pathogenesis of diabetic cardiomyopathy.	[99,107,112,113]
The myocardial tissue of diabetic hamsters	Chymase-specific inhibitor (TEI-F00806/TEI-E00548)	Chymase/Ang II	8-OHdG↓, Nox4↓, Ang II↓, fibrosis indexes↓	Chymase inhibition might prevent oxidative stress and diabetic cardiomyopathy at an early stage by reducing local AngII production.	[107]
Diabetic mice	–	FOXO1	KLF5↑, Nox4↑, ceramide accumulation and cardiac dysfunction	KLF5 is a new therapeutic target for the prevention and treatment of diabetic cardiomyopathy.	[119]
STZ-induced diabetic mice	Cardiac-specific overexpression of JunD	JunD	Nox4、NF-κB and other mediators of oxidative stress and inflammation↓, aberrant epigenetic regulation and cardiac dysfunction↓	Pave the way for tissue-specific therapeutic modulation of JunD to prevent diabetic cardiomyopathy.	[104]