Knockdown of lysyl oxidase like 1 inhibits the proliferation and pro-fibrotic effects of transforming growth factor-ß1-induced hypertrophic scar fibroblasts.

Ying, Mengxia; Chen, Yan; Yuan, Bo

Ying, Mengxia; Chen, Yan; Yuan, Bo.

Afiliación

Ying M; Department of Dermatology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo City, Zhejiang Province 315020, China.
Chen Y; Department of Dermatology, Ningbo Medical Center Lihuili Hospital, Ningbo City, Zhejiang Province 315040, China.
Yuan B; Department of Dermatology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo City, Zhejiang Province 315020, China.

Can J Physiol Pharmacol ; 99(12): 1272-1279, 2021 Dec.

Article en En | MEDLINE | ID: mdl-34283938

RESUMEN

The excessive healing response during wound repair can result in hypertrophic scars (HS). Lysyl oxidase like 1 (LOXL1) has been reported to be associated with fibrosis via targeting transforming growth factor ß1 (TGF-ß1) signaling. This study aimed to investigate the effect of LOXL1 on HS formation. The expression of LOXL1 in HS tissues and TGF-ß1-induced HS-derived fibroblasts (HSFs) was detected via reverse transcription quantitative PCR and Western blot. LOXL1 was silenced in HSFs using transfection with short hairpin RNA (shRNA), then wound healing process including cell proliferation, cell cycle distribution, migration, and extracellular matrix (ECM) deposition along with Smad expression were measured by cell counting kit-8, EdU staining, flow cytometry, transwell, immunofluorescence, and Western blot assays. LOXL1 was upregulated in HS tissues and TGF-ß1-induced HSFs. Knockdown of LOXL1 inhibited proliferation and migration but promoted cell cycle G0/G1 phase arrest in TGF-ß1-induced HSFs; it increased expression of cyclin D1, CDK4, MMP2, MMP9, COL1A1, COL1A2, fibronectin, COL3A1, α-SMA, but decreased expression of p27, and the phosphorylation of Smad2 and Smad3 caused by TGF-ß1 were also blocked by LOXL1 silencing. Silence of LOXL1 could effectively inhibit TGF-ß1-induced proliferation, migration, and ECM deposition in HSFs via inactivating Smad pathway. Targeting LOXL1 may have future therapeutic implications for HS treatment.

Asunto(s)

Aminoácido Oxidorreductasas/genética; Aminoácido Oxidorreductasas/fisiología; Proliferación Celular/genética; Fibroblastos/patología; Fibrosis/genética; Técnicas de Silenciamiento del Gen; Silenciador del Gen; Transducción de Señal/genética; Transducción de Señal/fisiología; Factor de Crecimiento Transformador beta1/fisiología; Adulto; Movimiento Celular/genética; Matriz Extracelular/metabolismo; Femenino; Humanos; Masculino; Persona de Mediana Edad; Fosforilación; Proteína Smad2/metabolismo; Proteína smad3/metabolismo; Cicatrización de Heridas/genética; Cicatrización de Heridas/fisiología

Palabras clave

Smad; Transforming growth factor-ß1; cicatrice hypertrophique; facteur de croissance transformant ß1; hypertrophic scar; lysyl oxidase like 1; lysyl oxidase like 1; protéines Smad

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fibrosis / Transducción de Señal / Silenciador del Gen / Proliferación Celular / Factor de Crecimiento Transformador beta1 / Técnicas de Silenciamiento del Gen / Fibroblastos / Aminoácido Oxidorreductasas Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Can J Physiol Pharmacol Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Canadá

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