Resistin-like molecules: a marker, mediator and therapeutic target for multiple diseases

Shi, Yaning; Zhu, Neng; Qiu, Yun; Tan, Junlan; Wang, Feiying; Qin, Li; Dai, Aiguo

doi:10.1186/s12964-022-01032-w

Cell Communication and Signaling

Table 3 Diseases and related mechanisms regulated by RELMβ

From: Resistin-like molecules: a marker, mediator and therapeutic target for multiple diseases

RELMs	Cell type	Animal type	Stimulator	Signaling pathways	Effector molecules	Effect	Diseases	References
RELMβ	Human PASMCs	SD rats	NA	PI3K/Akt/mTOR pathway and PKC/MAPK pathway	Ca²⁺↑, p-PI3K↑, p-Akt↑, p-mTOR↑, p-PKC↑ and p-MAPK↑	PASMCs proliferation	PH	[28, 57]
RELMβ	Human PASMCs	NA	NA	KCNK3 pathway	KCNK3↓and p-STAT3↑	PASMCs proliferation	PH	[58]
RELMβ	Human PASMCs	NA	NA	FAK-survivin pathway	FAK↑ and survivin↑	PASMCs proliferation	PH	[59]
RELMβ	Human BECs	NA	NA	ERK1/2 pathway and PI3K/Akt pathway	p-ERK1/2↑, p-PI3K↑, p-Akt↑, TGF-β2↑, EGF↑, VEGF↑ and MUC5AC↑	BECs proliferation and airway remodelling	Asthma	[60]
RELMβ	Human lung fibroblasts	RELMβ^−/− C57BL/6 mice	NA	NA	TGF-β1↑, TGF-β2↑, collagen I↑, fibronectin↑, α-SMA↑, laminin α1↑, Hapl1↑ and p-ERK1/2↑	Proliferation of human lung fibroblasts and airway remodelling	Asthma	[61]
RELMβ	NIH/3T3 cell line and human lung fibroblasts	Mice deficient in STAT6 or IL-4 and IL-13 in the BALB/c background	OVA and Aspergillus fumigatus	IL-13 pathway and STAT6 pathway	IL-4↑, IL-13↑ and STAT6↑	Airway inflammation and lung remodeling	Asthma	[79]
RELMβ	NA	RELMβ^−/− C57BL/6 mice	Aspergillus fumigatus	NA	TNFα↓, VEGF↓, IFNγ↓ and IL-13↓	Preventing inflammation, goblet cell metaplasia, subepithelial fibrosis and airway resistance	Asthma	[81]
RELMβ	Human UVECs and human PAECs	NA	NA	TGF-β1/SMAD2/3/4 pathway	TGF-β1↑ and SMAD2/3/4↑	EndMT, proliferation and migration of human UVECs and human PAECs	Pulmonary fibrosis	[31]
RELMβ	Rat AECs, human airway epithelial cells and mouse lung fibroblast	RELMβ KO mice	BLM	STAT6 pathway and ERK pathway	Collagen type I↑ and α-SMA↑	Stimulation of fibroblast proliferation, promotion of myofibroblast differentiation, and the recruitment of BMD cells to the lung	Pulmonary fibrosis	[86]
RELMβ	Macrophage and CD4⁺ T cells	RELMβ^−/− mice	Trichuris muris	NA	TNF-α↑, IL-6↑, IL-12/23p40↑ and IFN-γ↑	Intestinal inflammation	Intestinal inflammation	[51]
RELMβ	NA	RELMβ^−/− mice	DSS	NA	NA	Colitis	Colitis	[47, 48]
RELMβ	NA	Muc2^−/−/RELMβ^−/− C57BL/6 mice	NA	NA	RegIIIβ↑	Colitis and antibacterial	Colitis	[49]
RELMβ	NA	RELMβ^−/− C57BL/6 mice	C. rodentium	NA	IL-22↑	IECs proliferation and limiting the intestinal damage	Colitis	[63]
RELMβ	BMD macrophage of mice	SAMP1/YitFc mice	NA	NA	TNF-α↑, IL-6↑ and CCL5↑	Ileitis	Ileitis	[50]
RELMβ	Human colon cancer cells	C57BL/6 J mice	Trinitrobenzene sulfonic acid	PKC pathway and tyrosine kinases pathway	p-ERK1/2↑, MUC2↑ and M1/MUC5AC↑	Maintaining the mucosal defense barrier	Colitis	[70]
RELMβ	NA	IL-33–deficient C57BL/6 mice	N. brasiliensis	NA	IL-13↑ and IL-33↑	Recruiting eosinophils and eliminating parasite	Hookworm Infection	[94]
RELMβ	Human colon cancer cells	IL-4^–/– mice and IL-4Rα^–/– mice	Trichuris spiralis, N. brasiliensis, Trichinella muris and Strongyloides stercoralis	NA	IL-13↑	Inhibiting nematode chemotaxis	GI nematode infection	[95]
RELMβ	Human colon cancer cells	NA	S. aureus	NA	NA	Destroying the bacterial cytoplasm	S. aureus infection	[97]
RELMβ	Hepatocyteof mice	RELMβ transgenic C57BL/6 mice	High fat	MAPKs pathways	IRS-1↓, IRS-2↓, p-ERK1/2↑, p-p38 MAPK↑ and p-JNK↑	Hyperglycemia, hyperlipidemia, fatty liver, pancreatic islet enlargement and hepatic insulin resistance	Diabetes	[65]
RELMβ	NA	Wistar rats, C57BL/6 J mice	Glucose	PKC βII pathway and AMPK pathway	SGLT-1↓, GLUT2↑, PKC βII↑ and p-AMPK↑	Promotion of intestinal glucose absorption	Diabetes	[67]
RELMβ	Human aortic VSMCs	NA	High glucose	ERK1/2 pathway and p38 MAPK pathway	α-SMA↓, SM-MHC↓, calponin↓, OPN↑, p-ERK1/2↑ and p-p38 MAPK↑	VSMCs proliferation	Atherosclerosis	[62]
RELMβ	Macrophag from mice	RELMβ^−/− ApoE^−/− mice and RELMβ^−/− LDLR^−/− mice	High cholesterol	NA	VLDLR↑, SR-A1↑ ABCA1↑, ABCG1↓, TNFα↑, IL-1β↑, IL-6↑ and p-NF-κB↑	Formation of macrophage derived foam cell and inflammation	Atherosclerosis	[103]
RELMβ	Gastric carcinoma cells and normal gastric mucosa epithelial cells	NA	NA	NA	N-cadherin↑, Snail↑, Vimentin↑ and E-cadherin↓	Invasion and migration of gastric carcinoma cells	Gastric carcinoma	[110]
RELMβ	Macrophages of mice	RELMβ-KO mice	MCD and LPS	TLR4 pathway	TLR4↑, TNF-α↑, IL-1β↑ and IL-6↑	Lipid accumulation, inflammation and liver fibrosis	NASH	[120]

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