Last update 19 Sep 2024

SRF

Last update 19 Sep 2024

Basic Info

Synonyms

MCM1, serum response factor, SRF

Introduction

SRF is a transcription factor that binds to the serum response element (SRE), a short sequence of dyad symmetry located 300 bp to the 5' of the site of transcription initiation of some genes (such as FOS). Together with MRTFA transcription coactivator, controls expression of genes regulating the cytoskeleton during development, morphogenesis and cell migration. The SRF-MRTFA complex activity responds to Rho GTPase-induced changes in cellular globular actin (G-actin) concentration, thereby coupling cytoskeletal gene expression to cytoskeletal dynamics. Required for cardiac differentiation and maturation.

Drugs associated with SRF

CCG-232964

Target

MRTFB x RP4 x SRF

Mechanism

MRTFB inhibitors [+2]

Active Org.

University of Michigan

Originator Org.

University of Michigan

Active Indication

Scleroderma, Systemic

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

CCG-203971

Target

SRF

Mechanism

SRF inhibitors

Active Org.

Genesis Biosciences LLC [+1]

Originator Org.

Genesis Biosciences LLC

Active Indication

Diabetes Mellitus, Type 2

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with SRF

100 Translational Medicine associated with SRF

0 Patents (Medical) associated with SRF

3,562

Literatures (Medical) associated with SRF

01 Dec 2024·Cellular and Molecular Life Sciences

Vascular injury activates the ELK1/SND1/SRF pathway to promote vascular smooth muscle cell proliferative phenotype and neointimal hyperplasia

Article

Author: Wei, Minxin ; Xin, Lingbiao ; Ma, Jinzheng ; Hao, Wei ; Liu, Mingxia ; Su, Chao ; Yu, Ying ; Ren, Yuanyuan ; Gao, Xingjie ; Yang, Jie ; Ge, Lin ; Yao, Xuyang

AbstractBackgroundVascular smooth muscle cell (VSMC) proliferation is the leading cause of vascular stenosis or restenosis. Therefore, investigating the molecular mechanisms and pivotal regulators of the proliferative VSMC phenotype is imperative for precisely preventing neointimal hyperplasia in vascular disease.MethodsWire-induced vascular injury and aortic culture models were used to detect the expression of staphylococcal nuclease domain-containing protein 1 (SND1). SMC-specific Snd1 knockout mice were used to assess the potential roles of SND1 after vascular injury. Primary VSMCs were cultured to evaluate SND1 function on VSMC phenotype switching, as well as to investigate the mechanism by which SND1 regulates the VSMC proliferative phenotype.ResultsPhenotype-switched proliferative VSMCs exhibited higher SND1 protein expression compared to the differentiated VSMCs. This result was replicated in primary VSMCs treated with platelet-derived growth factor (PDGF). In the injury model, specific knockout of Snd1 in mouse VSMCs reduced neointimal hyperplasia. We then revealed that ETS transcription factor ELK1 (ELK1) exhibited upregulation and activation in proliferative VSMCs, and acted as a novel transcription factor to induce the gene transcriptional activation of Snd1. Subsequently, the upregulated SND1 is associated with serum response factor (SRF) by competing with myocardin (MYOCD). As a co-activator of SRF, SND1 recruited the lysine acetyltransferase 2B (KAT2B) to the promoter regions leading to the histone acetylation, consequently promoted SRF to recognize the specific CArG motif, and enhanced the proliferation- and migration-related gene transcriptional activation.ConclusionsThe present study identifies ELK1/SND1/SRF as a novel pathway in promoting the proliferative VSMC phenotype and neointimal hyperplasia in vascular injury, predisposing the vessels to pathological remodeling. This provides a potential therapeutic target for vascular stenosis.Graphical abstract

01 Dec 2024·Cellular and Molecular Life Sciences

Direct GPCR-EGFR interaction enables synergistic membrane-to-nucleus information transfer

Article

Author: Robaa, Dina ; Braun, Heike ; Olgac, Abdurrahman ; Schreier, Barbara ; Eckenstaler, Robert ; Gekle, Michael ; Benndorf, Ralf ; Dubourg, Virginie ; Sippl, Wolfgang ; Mildenberger, Sigrid

AbstractWe addressed the heteromerization of the epidermal growth factor receptor (EGFR) with G-protein coupled receptors (GPCR) on the basis of angiotensin-II-receptor-subtype-1(AT1R)-EGFR interaction as proof-of-concept and show its functional relevance during synergistic nuclear information transfer, beyond ligand-dependent EGFR transactivation. Following in silico modelling, we generated EGFR-interaction deficient AT1R-mutants and compared them to AT1R-wildtype. Receptor interaction was assessed by co-immunoprecipitation (CoIP), Förster resonance energy transfer (FRET) and fluorescence-lifetime imaging microscopy (FLIM). Changes in cell morphology, ERK1/2-phosphorylation (ppERK1/2), serum response factor (SRF)-activation and cFOS protein expression were determined by digital high content microscopy at the single cell level. FRET, FLIM and CoIP confirmed the physical interaction of AT1R-wildtype with EGFR that was strongly reduced for the AT1R-mutants. Responsiveness of cells transfected with AT1R-WT or –mutants to angiotensin II or EGF was similar regarding changes in cell circularity, ppERK1/2 (direct and by ligand-dependent EGFR-transactivation), cFOS-expression and SRF-activity. By contrast, the EGFR-AT1R-synergism regarding these parameters was completely absent for in the interaction-deficient AT1R mutants. The results show that AT1R-EGFR heteromerisation enables AT1R-EGFR-synergism on downstream gene expression regulation, modulating the intensity and the temporal pattern of nuclear AT1R/EGFR-information transfer. Furthermore, remote EGFR transactivation, via ligand release or cytosolic tyrosine kinases, is not sufficient for the complete synergistic control of gene expression.

01 Dec 2024·Annals of Vascular Surgery

Influence of Proximal Fixation on Aneurysm Neck Evolution after Endovascular Treatment of Infrarenal Aneurysms

Article

Author: Iranzo, Noemí Hidalgo ; Alconchel, Laura Pastor ; Nieto, Beatriz García ; Medrano, Mónica Herrando ; Inaraja Pérez, Gabriel Cristian ; Marzo Álvarez, Ana Cristina

OBJECTIVEWe analyzed the long-term influence of fixation systems on proximal aortic neck (PAN) evolution by comparing two late-generation endoprostheses, Endurant (Medtronic Vascular, Minneapolis, Minn) with suprarenal fixation (SRF) and Excluder (W.L Gore & Associates, Flagstaff, Ariz) with infrarenal fixation (IRF).METHODSOur retrospective observational study included consecutive patients undergoing EVAR for aorto-iliac aneurysms (2011-2020). Primary end points: neck enlargement and freedom from significative PAN enlargement (5 mm). Secondary end points: neck-related reintervention, endoleaks and graft migration. Results were reported following the Society of Vascular Surgery reporting standards.RESULTS139 patients were included (97 in SRF group and 42 in IRF group). A difference in growth at 10 mm caudal to lowest renal artery at 2 years follow-up was found (mean growth of 1.92 ± 3.38 mm in SRF and 0.16 ± 6.86 mm in IRF; p <.001). A tendency to a major growth in SRF at 4 years follow-up at the lowest renal artery (1.27 ± 3.36 mm vs 0.63 ± 2.2 mm; p = .06), 5 mm distal to lowest renal artery (2.17 ± 3.52 mm vs 0.94 ± 2.76 mm; p =.001) and 10 mm distal to lowest renal artery (2.65 ± 3.86 mm vs 1.12 ± 1.5 mm; p <.001) was shown. Freedom from PAN enlargement was 96.65% and 88.20% in SRF and 100% and 94.4% in IRF at 2 and 4 years follow up respectively (log rank .041). A greater incidence of type II endoleaks in IRF was observed (40.48% vs 15.46%;p =.001). Oversizing > 15% showed to be a risk factor of PAN enlargement (OR 6.85; 95% IC 1.67 - 28.4; p =.007).CONCLUSIONSA small but significative percentage of patients after EVAR show a progressive PAN enlargement, being significatively greater in SRF, without increasing neck related complications four years after graft deployment.

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SRF

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