Physiological Effects of Ferroptosis on Organ Fibrosis

Table 1

The role of ferroptosis in fibrosis.

Organ	Mechanism	Molecular foundation	Ref
Liver	Iron overload-induced toxicity	Iron distribution disorder: iron in hepatocytes is excreted into adjacent HSCs through extracellular vesicles.	[46]
		Iron overload promotes ferroptosis in hepatocytes by inducing HO-1 overexpression.	[55]
		Trf-TFR1 mediates iron accumulation and causes ferroptosis in hepatocytes.	[57]
		Zip14-mediated accumulation of NTBI causes ferroptosis in hepatocytes with a Trf deficiency.	[57]
	Hepatic stellate cell activation	The RNA-binding protein ELAVL1/HuR induces HSC ferroptosis by regulating the autophagy pathway.	[58]
		The RNA-binding protein ZFP36/TTP protects against ferroptosis by regulating the autophagy signaling pathway in HSCs.	[86]
		Artemether ameliorates liver fibrosis by inhibiting HSC activation via p53-dependent ferroptosis.	[60]
		Artesunate ameliorates hepatic fibrosis by mediating HSC ferritinophagy.	[64]
		Magnesium isoglycyrrhizinate ameliorates hepatic fibrosis by inhibiting HSC activation via HO-1-mediated ferroptosis.	[65]
		Sorafenib attenuates liver fibrosis by triggering hepatic stellate cell ferroptosis via the HIF-1α/SLC7A11 pathway.	[120]
		Wogonoside alleviates liver fibrosis by inducing SOCS1/P53/SLC7A11-mediated HSC ferroptosis.	[122]
		The BRD7-P53-SLC25A28 axis plays an important role in the ferroptosis of HSCs.	[67]
	Activation of inflammation	Ferroptotic cells release DAMPs to exacerbate tissue inflammation and fibrosis.	[44]
Lung	Fibroblast-to-myofibroblast differentiation	GPX4 inhibits and upregulates TGF-β signaling to promote pulmonary fibrosis.	[76]
		Erastin promotes fibroblast-to-myofibroblast differentiation by increasing lipid peroxidation and inhibiting GPX4 expression.	[77]
	Oxidative damage	Liproxstatin-1 activates the Nrf2 pathway by weakening TGF-β expression to attenuate RILF.	[81]
		DHQ exerts antifibrotic effects by inhibiting ferroptosis through the downregulation of LC3 and upregulation of FTH1 and NCOA4 in activated HBE cells.	[101]
	Activation of inflammation	Accumulating inflammatory macrophages induce AT2 cell ferroptosis via the ALOX5-LTB4-ACSL4 axis.	[91]
Kidney	Activation of inflammation	Ferroptotic cells release profibrotic factors (TGF-β, CTGF, and PDGF).	[105]
		Accumulation of proinflammatory PT cells significantly downregulates GSH to increase inflammation and fibrosis.	[106]
		Tectorigenin alleviates fibrosis by inhibiting ferroptosis in TECs through the Smad3-NOX4 pathway.	[46]
Heart	Oxidative damage	MLK3-JNK/p53 pathway-mediated oxidative stress and ferroptosis cause myocardial fibrosis.	[111]
		Astragaloside IV inhibits adriamycin-induced cardiac ferroptosis by enhancing Nrf2 signaling.	[113]
		Elabela antagonizes ferroptosis by regulating the IL-6/STAT3/GPX4 signaling pathway to prevent adverse myocardial remodeling.	[112]
Submandibular gland	Activation of inflammation	Ferroptotic cells accelerate salivary gland fibrosis by secreting IL-1 and TNF-α.	[118]