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Periostin regulates lysyl oxidase through ERK1/2 MAPK-dependent serum response factor in activated cardiac fibroblasts.
Radhakrishnan, Sruthi; Shenoy, Sachin J; Devidasan, Indraja; Shaji, Binchu V; Gopal, Sarayu; Sreekumaran, Sreekanth; Sp, Abhilash; Sivaraman, Divya M; Mohan, Neethu.
Afiliación
  • Radhakrishnan S; Department of Pathology, Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.
  • Shenoy SJ; Department of Applied Biology, Division of In-Vivo Models and Testing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.
  • Devidasan I; Department of Pathology, Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.
  • Shaji BV; Department of Pathology, Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.
  • Gopal S; Department of Pathology, Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.
  • Sreekumaran S; Department of Pathology, Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.
  • Sp A; Department of Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.
  • Sivaraman DM; Department of Pathology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.
  • Mohan N; Department of Pathology, Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.
Cell Biochem Funct ; 42(4): e4066, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38822669
ABSTRACT
Collagen crosslinking, mediated by lysyl oxidase, is an adaptive mechanism of the cardiac repair process initiated by cardiac fibroblasts postmyocardial injury. However, excessive crosslinking leads to cardiac wall stiffening, which impairs the contractile properties of the left ventricle and leads to heart failure. In this study, we investigated the role of periostin, a matricellular protein, in the regulation of lysyl oxidase in cardiac fibroblasts in response to angiotensin II and TGFß1. Our results indicated that periostin silencing abolished the angiotensin II and TGFß1-mediated upregulation of lysyl oxidase. Furthermore, the attenuation of periostin expression resulted in a notable reduction in the activity of lysyl oxidase. Downstream of periostin, ERK1/2 MAPK signaling was found to be activated, which in turn transcriptionally upregulates the serum response factor to facilitate the enhanced expression of lysyl oxidase. The periostin-lysyl oxidase association was also positively correlated in an in vivo rat model of myocardial infarction. The expression of periostin and lysyl oxidase was upregulated in the collagen-rich fibrotic scar tissue of the left ventricle. Remarkably, echocardiography data showed a reduction in the left ventricular wall movement, ejection fraction, and fractional shortening, indicative of enhanced stiffening of the cardiac wall. These findings shed light on the mechanistic role of periostin in the collagen crosslinking initiated by activated cardiac fibroblasts. Our findings signify periostin as a possible therapeutic target to reduce excessive collagen crosslinking that contributes to the structural remodeling associated with heart failure.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Moléculas de Adhesión Celular / Ratas Sprague-Dawley / Fibroblastos / Proteína-Lisina 6-Oxidasa Límite: Animals Idioma: En Revista: Cell Biochem Funct Año: 2024 Tipo del documento: Article País de afiliación: India

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Moléculas de Adhesión Celular / Ratas Sprague-Dawley / Fibroblastos / Proteína-Lisina 6-Oxidasa Límite: Animals Idioma: En Revista: Cell Biochem Funct Año: 2024 Tipo del documento: Article País de afiliación: India