Evidence map›Paper›PMID 41873540›Full record

ArticleHypertension (Dallas, Tex. : 1979)2026

THBS4 Regulates Pulmonary Hypertension via TGF-β/SMAD2 Signaling.

Jie Zeng, Dengyuan Li, Jun Wang, Rong Wang, Zhenming Huang, Dan Bai, Xiaohua Liu, Dangxiong Sun, Gaohui Fu, Kang Kang and 7 more

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Article in Hypertension (Dallas, Tex. : 1979), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

17 authors.

Jie Zeng *Department of Pulmonary and Critical Care Medicine, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, China (J.Z., D.L., R.W., Z.H., D.S., R.L., Y.Z.).ORCID 0000-0003-3408-9384
Dengyuan Li *Department of Pulmonary and Critical Care Medicine, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, China (J.Z., D.L., R.W., Z.H., D.S., R.L., Y.Z.).
Jun Wang *Shenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, Guangdong, China (J.W., D.B., Xiaohua Liu, G.F., K.K., Xiaojia Liu, L.Y., F.Z., L.L., D.G.).ORCID 0000-0002-5470-4631
Rong WangDepartment of Pulmonary and Critical Care Medicine, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, China (J.Z., D.L., R.W., Z.H., D.S., R.L., Y.Z.).
Zhenming HuangDepartment of Pulmonary and Critical Care Medicine, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, China (J.Z., D.L., R.W., Z.H., D.S., R.L., Y.Z.).ORCID 0009-0002-5145-9703
Dan BaiShenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, Guangdong, China (J.W., D.B., Xiaohua Liu, G.F., K.K., Xiaojia Liu, L.Y., F.Z., L.L., D.G.).
Xiaohua LiuShenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, Guangdong, China (J.W., D.B., Xiaohua Liu, G.F., K.K., Xiaojia Liu, L.Y., F.Z., L.L., D.G.).ORCID 0009-0008-0113-3063
Dangxiong SunDepartment of Pulmonary and Critical Care Medicine, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, China (J.Z., D.L., R.W., Z.H., D.S., R.L., Y.Z.).ORCID 0000-0002-5196-8199
Gaohui FuShenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, Guangdong, China (J.W., D.B., Xiaohua Liu, G.F., K.K., Xiaojia Liu, L.Y., F.Z., L.L., D.G.).ORCID 0009-0009-0599-6146
Kang KangShenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, Guangdong, China (J.W., D.B., Xiaohua Liu, G.F., K.K., Xiaojia Liu, L.Y., F.Z., L.L., D.G.).ORCID 0000-0002-2080-2153
Xiaojia LiuShenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, Guangdong, China (J.W., D.B., Xiaohua Liu, G.F., K.K., Xiaojia Liu, L.Y., F.Z., L.L., D.G.).
Liu YangShenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, Guangdong, China (J.W., D.B., Xiaohua Liu, G.F., K.K., Xiaojia Liu, L.Y., F.Z., L.L., D.G.).
Feilong ZhaoShenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, Guangdong, China (J.W., D.B., Xiaohua Liu, G.F., K.K., Xiaojia Liu, L.Y., F.Z., L.L., D.G.).
Lingjie LuoShenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, Guangdong, China (J.W., D.B., Xiaohua Liu, G.F., K.K., Xiaojia Liu, L.Y., F.Z., L.L., D.G.).ORCID 0009-0001-8595-4342
Rufang LiDepartment of Pulmonary and Critical Care Medicine, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, China (J.Z., D.L., R.W., Z.H., D.S., R.L., Y.Z.).
Yunhui ZhangDepartment of Pulmonary and Critical Care Medicine, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, China (J.Z., D.L., R.W., Z.H., D.S., R.L., Y.Z.).ORCID 0000-0003-4545-2863
Deming GouShenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, Guangdong, China (J.W., D.B., Xiaohua Liu, G.F., K.K., Xiaojia Liu, L.Y., F.Z., L.L., D.G.).ORCID 0000-0002-3312-841X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPulmonary hypertension (PH) is a progressive disease marked by pulmonary arterial remodeling and right ventricular dysfunction. The molecular mechanisms driving this remodeling, particularly ECM (extracellular matrix)-mediated processes, remain poorly understood. This study investigates THBS4 (thrombospondin-4), an ECM glycoprotein, as a key regulator of pulmonary vascular remodeling in pulmonary hypertension.

methodsWhole-transcriptomic analysis was conducted on pulmonary arteries from rat models of pulmonary hypertension induced by hypoxia, hypoxia-SUGEN, and monocrotaline. THBS4 expression was measured in these models and in serum and lung tissue from patients with pulmonary arterial hypertension. The role of HIF-1α (hypoxia-inducible factor 1-alpha), SMAD2 (mothers against decapentaplegic homolog 2), and p38 MAPK (mitogen-activated protein kinase) signaling pathways in regulating THBS4 was explored. Functional assays assessed THBS4's impact on pulmonary artery smooth muscle cells. In vivo, THBS4 silencing was performed to evaluate its effect on vascular remodeling and right ventricular hypertrophy.

resultsTHBS4 was upregulated in pulmonary arteries across all pulmonary hypertension models, with expression correlating with disease severity. Elevated THBS4 levels were observed in pulmonary arterial hypertension patient serum and lung tissue. Hypoxia-induced THBS4 expression was mediated by HIF-1α, while TGF (transforming growth factor)-β1 stimulation enhanced THBS4 via SMAD2 and p38 MAPK pathways. THBS4 promoted pulmonary artery smooth muscle cell proliferation, phenotypic modulation, and ECM remodeling. In vivo silencing of THBS4 attenuated pulmonary vascular remodeling and right ventricular hypertrophy.

conclusionsOur findings identify THBS4 as a central regulator in a self-reinforcing THBS4-TGF-β/SMAD2 signaling axis driving pulmonary vascular remodeling. Targeting THBS4 represents a promising therapeutic strategy to mitigate pathological vascular remodeling in pulmonary hypertension.

Indexed as

Hypertension, PulmonarySmad2 ProteinThrombospondinsTransforming Growth Factor betaAnimalsDisease Models, AnimalHumansHypoxiaHypoxia-Inducible Factor 1, alpha SubunitMalePulmonary ArteryRatsRats, Sprague-DawleySignal TransductionVascular RemodelingHypoxia-Inducible Factor 1, alpha SubunitSmad2 ProteinSmad2 protein, ratthrombospondin 4ThrombospondinsTransforming Growth Factor betaextracellular matrixhypertension, pulmonarySMAD2 proteinthrombospondinstransforming growth factor betavascular remodeling

Identifiers

PMID41873540
PMCPMC13189383

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