ArticleCell communication and signaling : CCS2014
Divergent signaling pathways cooperatively regulate TGFβ induction of cysteine-rich protein 2 in vascular smooth muscle cells.
Article in Cell communication and signaling : CCS, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 18 citations in OpenAlex.
- CSRP2 modulates PDGFRA/PI3K/AKT signaling via PRC1 components in glioma.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Cysteine‑ and glycine‑rich protein 2: A vital regulator that inhibits necroptosis glioma cell by activating the JAK‑STAT1 pathways.Oncology reports · 2025Article
- Role of CRP2-MRTF interaction in functions of myofibroblasts.Cell structure and function · 2023Article
- Transcriptomic and physiological analyses reveal temporal changes contributing to the delayed healing response to arterial injury in diabetic rats.JVS-vascular science · 2023Article
- Significance of the p38MAPK-CRP2 axis in myofibroblastic phenotypic transition.Cell structure and function · 2023Article
- Amyloidogenic Processing of Amyloid Precursor Protein Drives Stretch-Induced Disruption of Axonal Transport in hiPSC-Derived Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Fetuin-B regulates vascular plaque rupture via TGF-β receptor-mediated Smad pathway in vascular smooth muscle cells.Pflugers Archiv : European journal of physiology · 2020Article
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- Prostaglandin EAmerican journal of physiology. Lung cellular and molecular physiology · 2019Article
- Loss of heme oxygenase-1 accelerates mesodermal gene expressions during embryoid body development from mouse embryonic stem cells.Redox biology · 2018Article
- Involvement of Rho-associated coiled-coil kinase signaling inhibition in TGF-β1/Smad2, 3 signal transductionInternational journal of ophthalmology · 2017Article
- CRP2, a new invadopodia actin bundling factor critically promotes breast cancer cell invasion and metastasis.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundVascular smooth muscle cells (VSMCs) of the arterial wall play a critical role in the development of occlusive vascular diseases. Cysteine-rich protein 2 (CRP2) is a VSMC-expressed LIM-only protein, which functionally limits VSMC migration and protects against pathological vascular remodeling. The multifunctional cytokine TGFβ has been implicated to play a role in the pathogenesis of atherosclerosis through numerous downstream signaling pathways. We showed previously that TGFβ upregulates CRP2 expression; however, the detailed signaling mechanisms remain unclear.
resultsTGFβ treatment of VSMCs activated both Smad2/3 and ATF2 phosphorylation. Individually knocking down Smad2/3 or ATF2 pathways with siRNA impaired the TGFβ induction of CRP2, indicating that both contribute to CRP2 expression. Inhibiting TβRI kinase activity by SB431542 or TβRI knockdown abolished Smad2/3 phosphorylation but did not alter ATF2 phosphorylation, indicating while Smad2/3 phosphorylation was TβRI-dependent ATF2 phosphorylation was independent of TβRI. Inhibiting Src kinase activity by SU6656 suppressed TGFβ-induced RhoA and ATF2 activation but not Smad2 phosphorylation. Blocking ROCK activity, the major downstream target of RhoA, abolished ATF2 phosphorylation and CRP2 induction but not Smad2 phosphorylation. Furthermore, JNK inhibition with SP600125 reduced TGFβ-induced ATF2 (but not Smad2) phosphorylation and CRP2 protein expression while ROCK inhibition blocked JNK activation. These results indicate that downstream of TβRII, Src family kinase-RhoA-ROCK-JNK signaling pathway mediates TβRI-independent ATF2 activation. Promoter analysis revealed that the TGFβ induction of CRP2 was mediated through the CRE and SBE promoter elements that were located in close proximity.
conclusionsOur results demonstrate that two signaling pathways downstream of TGFβ converge on the CRE and SBE sites of the Csrp2 promoter to cooperatively control CRP2 induction in VSMCs, which represents a previously unrecognized mechanism of VSMC gene induction by TGFβ.
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