PDF(Pubmed)
Abstract：
UNASSIGNED: Hypertrophic scarring (HS) is commonly described as an abnormal post-traumatic tissue repair characterized by excessive hypercellularity and extracellular matrix (ECM) deposition. Mounting evidence suggests that MALAT1 is maladjusted in many fibrotic diseases, but its contribution to HS progression remains poorly understood. Hence, we sought to elucidate the fundamental role of MALAT1 in HS.
UNASSIGNED: The expression of MALAT1, miR-29a-3p, and Smurf2 in skin tissues and fibroblasts was assessed by RT-qPCR and Western blotting. Furthermore, lentiviruses, RNAi, or plasmids were utilized to transfect hypertrophic scar fibroblasts (HSFs) for gene overexpression or downregulation. The biological behaviors of HSFs were quantified by the CCK-8 assay, wound healing assay, transwell assay, and flow cytometry. Mechanistically, bioinformatics analysis, dual-luciferase reporter assays, and rescue experiments were performed to verify the relationship between miR-29a-3p and MALAT1 or Smurf2.
UNASSIGNED: Our data indicate that MALAT1, Smurf2 were overexpressed while miR-29a-3p was suppressed in HS tissues and fibroblasts. Downregulation of MALAT1 may lead to decreased proliferation, migration, and invasion of fibroblasts, accompanied by enhanced apoptosis, reduced TGF-β signal transduction, and ECM accumulation in HSFs, by enhancing miR-29a-3p and suppressing Smurf2 expression. Mechanistically, MALAT1 acted as a sponge for miR-29a-3p, while miR-29a-3p directly targeted Smurf2. More importantly, rescue experiments suggested that MALAT1 downregulation induced impact on the proliferation, migration, and invasion of HSFs could be partially overturned through miR-29a-3p knockdown or Smurf2 overexpression.
UNASSIGNED: MALAT1 knockdown inhibits the proliferation, migration, invasion, and collagen deposition of HSFs via targeting the miR-29a-3p/Smurf2 axis, which may reveal a promising therapeutic exploitable vulnerability to HS.
UNASSIGNED: The expression of MALAT1, miR-29a-3p, and Smurf2 in skin tissues and fibroblasts was assessed by RT-qPCR and Western blotting. Furthermore, lentiviruses, RNAi, or plasmids were utilized to transfect hypertrophic scar fibroblasts (HSFs) for gene overexpression or downregulation. The biological behaviors of HSFs were quantified by the CCK-8 assay, wound healing assay, transwell assay, and flow cytometry. Mechanistically, bioinformatics analysis, dual-luciferase reporter assays, and rescue experiments were performed to verify the relationship between miR-29a-3p and MALAT1 or Smurf2.
UNASSIGNED: Our data indicate that MALAT1, Smurf2 were overexpressed while miR-29a-3p was suppressed in HS tissues and fibroblasts. Downregulation of MALAT1 may lead to decreased proliferation, migration, and invasion of fibroblasts, accompanied by enhanced apoptosis, reduced TGF-β signal transduction, and ECM accumulation in HSFs, by enhancing miR-29a-3p and suppressing Smurf2 expression. Mechanistically, MALAT1 acted as a sponge for miR-29a-3p, while miR-29a-3p directly targeted Smurf2. More importantly, rescue experiments suggested that MALAT1 downregulation induced impact on the proliferation, migration, and invasion of HSFs could be partially overturned through miR-29a-3p knockdown or Smurf2 overexpression.
UNASSIGNED: MALAT1 knockdown inhibits the proliferation, migration, invasion, and collagen deposition of HSFs via targeting the miR-29a-3p/Smurf2 axis, which may reveal a promising therapeutic exploitable vulnerability to HS.
摘要：
■肥厚性瘢痕形成(HS)通常被描述为异常的创伤后组织修复,其特征在于过度的细胞增多和细胞外基质(ECM)沉积。越来越多的证据表明MALAT1在许多纤维化疾病中失调，但其对HS进展的贡献仍知之甚少。因此，我们试图阐明MALAT1在HS中的基本作用。
■MALAT1,miR-29a-3p,通过RT-qPCR和Western印迹评估皮肤组织和成纤维细胞中的Smurf2。此外，慢病毒,RNAi,或质粒用于转染肥厚性瘢痕成纤维细胞（HSF）以进行基因过表达或下调。通过CCK-8测定对HSF的生物学行为进行定量，伤口愈合试验，transwell分析，和流式细胞术。机械上,生物信息学分析，双荧光素酶报告分析，和挽救实验验证miR-29a-3p与MALAT1或Smurf2之间的关系。
■我们的数据表明在HS组织和成纤维细胞中MALAT1、Smurf2过表达,而miR-29a-3p被抑制。下调MALAT1可能导致增殖减少，迁移,和成纤维细胞的侵袭，伴随着增强的细胞凋亡，减少TGF-β信号转导，和ECM在HSF中的积累，通过增强miR-29a-3p和抑制Smurf2表达。机械上,MALAT1充当miR-29a-3p的海绵，而miR-29a-3p直接靶向Smurf2。更重要的是,拯救实验表明，MALAT1下调诱导增殖的影响，迁移,HSF的侵袭可以通过miR-29a-3p敲低或Smurf2过表达来部分推翻。
■MALAT1敲低抑制增殖，迁移,入侵,和HSF通过靶向miR-29a-3p/Smurf2轴的胶原沉积，这可能揭示了对HS的有希望的治疗可利用的脆弱性。
■MALAT1,miR-29a-3p,通过RT-qPCR和Western印迹评估皮肤组织和成纤维细胞中的Smurf2。此外，慢病毒,RNAi,或质粒用于转染肥厚性瘢痕成纤维细胞（HSF）以进行基因过表达或下调。通过CCK-8测定对HSF的生物学行为进行定量，伤口愈合试验，transwell分析，和流式细胞术。机械上,生物信息学分析，双荧光素酶报告分析，和挽救实验验证miR-29a-3p与MALAT1或Smurf2之间的关系。
■我们的数据表明在HS组织和成纤维细胞中MALAT1、Smurf2过表达,而miR-29a-3p被抑制。下调MALAT1可能导致增殖减少，迁移,和成纤维细胞的侵袭，伴随着增强的细胞凋亡，减少TGF-β信号转导，和ECM在HSF中的积累，通过增强miR-29a-3p和抑制Smurf2表达。机械上,MALAT1充当miR-29a-3p的海绵，而miR-29a-3p直接靶向Smurf2。更重要的是,拯救实验表明，MALAT1下调诱导增殖的影响，迁移,HSF的侵袭可以通过miR-29a-3p敲低或Smurf2过表达来部分推翻。
■MALAT1敲低抑制增殖，迁移,入侵,和HSF通过靶向miR-29a-3p/Smurf2轴的胶原沉积，这可能揭示了对HS的有希望的治疗可利用的脆弱性。
