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 2 Diseases and related mechanisms regulated by RELMα

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
RELMα	Rat PMVECs	C57BL/6 mice	NA	NA	VEGF↑, MCP-1↑, SDF-1↑ and VEGFR2↓	Proliferation and migration of PMVECs, and pulmonary inflammation	PH	[36]
RELMα	Macrophages of mice and HLFs	HIF-1α^+/+ and HIF-1α^+/− mice	NA	HIF-1/VEGF-A/VEGFR2 pathway and IKK-β/NF-κB/HIF-1 pathway	HIF-1α↑, VEGF-A↑, VEGFR2↓, NF-κB↑ and IL-6↑	Pulmonary vascular remodeling, vascular tube formation and BMD cells recruitment and pulmonary inflammation	PH	[37]
RELMα	NA	RELMα^−/−BALB/c mice	OVA	NA	(IL-1β, 1ra, 16, 17; CXCL1, 2, 9, 10, 13; MCP-1; M-CSF; TIMP-1 and TREM-1) ↑	Pulmonary vascular remodeling and pulmonary inflammation	PH	[38]
RELMα	Human macrophages	RELMα^−/−C57BL/6 mice	NA	HMGB1/RAGE pathway	HMGB1↑ and RAGE↑	Pulmonary inflammation	PH	[39]
RELMα	Mouse PMVECs	IL-4 KO C57BL/6 mice	NA	IL-4/IL-4Ri pathway	VEGF↑, MCP-1↑ and SDF-1↑	Proliferation and migration of PMVECs	PH	[24]
RELMα	Human PMVECs and human PVSMCs	RELMα KO C57BL/6 J mice	NA	HMGB1/RAGE pathway	HMGB1↑, RAGE↑ and BMPR2↓	Autophagy, and anti-apoptosis and proliferation of PVSMCs	PH	[53]
RELMα	Human bone marrow MSCs	RELMα^−/− BALB/c mice	NA	PI3K/Akt pathway and ERK1/2 pathway	p-Akt↑ and p-ERK1/2↑	Proliferation of non-hematopoietic progenitor cells and MSCs	PH	[54, 55]
RELMα	Neonatal rat cardiomyocytes	SD rats	NA	PGC-1α/PPARα/ERRα pathway	PGC-1α↓, PPARα↓, ERRα↓, TFAM↓, Top1mt↓, POLG2↓, Polrmt↓, LCAD↓, VLCAD↓, ACADM↓, ACADS↓, Cpt-1a↓ and Cpt-1b↓	Mediating cardiac energy metabolism and mitochondrial structure, biogenesis and function	PH and right ventricular hypertrophy	[74]
RELMα	NA	Retnla-Tg mice	OVA	NA	Muc5ac↓, IL-4↓, IL-5↓, IL-13↓ and p-ERK1/2↓	Preventing allergic lung inflammation	Asthma	[78]
RELMα	Rat AECII and Rat lung fibroblasts	Wistar rats and Fisher 344 rats	OVA and BLM	NA	α-SMA↑and collagen type I↑	Myofibroblast differentiation	Pulmonary fibrosis and asthma	[76, 77]
RELMα	BECs	RELMα^−/− C57BL/6 mice	OSM	NA	COL1A1↑, COL3A1↑, MMP13↑ and TIMP1↑	ECM remodelling	Pulmonary fibrosis	[84]
RELMα	NA	SD Rat	L-arginine and sodium taurocholate	NA	p-Akt↑, p-NF-κB↑, p-p38 MAPK↑, p-ERK↑, ICAM-1↑, IL-1β↑, IL-6↑, IL-8↑, TNF-α↑ and CRP↑	Inflammation and lung injury	APALI	[40]
RELMα	NA	BALB/c mice and BL/6 mice	N. brasiliensis	NA	IL-17A↓	Limiting emphysema	Emphysema	[42]
RELMα	NA	RELMα^−/− C57BL/6 mice	S. mansoni eggs	BTK pathway	IL-4↓, IL-5↓ and IL-13↓	Limiting pulmonary inflammation	NA	[41]
RELMα	NA	RELMα^−/− and IL-17A^−/− C57BL/6 mice	C. rodentium	IL-23p19/IL-17A pathway	IL-23p19↑ and IL-17A↑	Intestinal inflammation	Intestinal inflammation	[45, 46]
RELMα	BMD macrophage	RELMα^−/− C57BL/6 or BALB/c mice	DSS	NA	IL-5↑, IL-6↑, IL-10↓, IL-17↑, TNF-α↑, CCL5↑, CCL11↑, p-NF-κB↑, p-ERK1/2↑ and p-p38 MAPK↑	Colitis	Colitis	[43, 44]
RELMα	NA	RELMα^−/− and RELMβ^−/− mice	N. brasiliensis	Fc receptor signaling and STAT6 pathway	IL-4↓, IL-13↓ and IL-17A↓	Downregulating lung inflammation and delaying parasite expulsion	Hookworm Infection	[87, 89,90,91]
RELMα	Murine myoblast cell and human endothelial progenitor cell	NA	NA	PDK1/PI3K/Akt/c-Jun pathway	p-PDK1↑, p-PI3K↑, p-Akt↑, p–c-Jun↑ and IL-18↑	Formation of endothelial progenitor cell tube and angiogenesis	Inflammatory myopathy	[106]
RELMα	Mouse eosinophils and mouse epithelial cells	CC10-rtTA-RELMα bitransgenic mice	DOX	NA	NA	Epithelial cell hyperplasia and basal layer thickness	EoE	[56]
RELMα	VSMCs of rat	ApoE^–/–C57BL/6 J mice	High fat	NA	NA	Proliferation and migration of VSMCs	Atherosclerosis	[102]
RELMα	Murine AML-12 cells and peritoneal macrophage of mice	Retnla^−/− C57BL/6 J mice, Ldlr^−/−Retnla^−/− mice and Retnla-Tg mice	High fat	Lrh-1/CYP7A1 pathway	Lrh-1↑, CYP7A1↑ and VLDL cholesterol↓	Increasing excretion of cholesterol in the form of bile acids	Hypercholesterolaemia and atherosclerosis	[20]
RELMα	Mouse macrophages	ApoE^−/− mice	Ang II	ERK1/2 pathway and JNK pathway	MCP-1↑, IL-6↑, MMP-2↑, MMP-9↑, p-ERK1/2↑ and p-JNK↑	Vascular inflammation	Abdominal aortic aneurysm	[107]
RELMα	Gastric cancer cells	Human	NA	NF-κB-MMP-9/VEGF pathway	NF-κB↑, VEGF↑ and MMP-9↑	Proliferation, migration and invasion of gastric cancer cells	Gastric cancer	[108]

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