Exosomes derived from human hypertrophic scar fibroblasts induces smad and TAK1 signaling in normal dermal fibroblasts

Hui Song Cui; Dong Hyun Kim; So Young Joo; Yoon Soo Cho; June-Bum Kim; Cheong Hoon Seo

doi:10.1016/j.abb.2022.109215

Exosomes derived from human hypertrophic scar fibroblasts induces smad and TAK1 signaling in normal dermal fibroblasts

Arch Biochem Biophys. 2022 Jun 15:722:109215. doi: 10.1016/j.abb.2022.109215. Epub 2022 Apr 14.

Authors

Hui Song Cui¹, Dong Hyun Kim², So Young Joo³, Yoon Soo Cho³, June-Bum Kim⁴, Cheong Hoon Seo⁵

Affiliations

¹ Burn Institute, Department of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, 94-200 Yeong-deungpo-Dong, Yeongdeungpo-Ku, Seoul, 07247, South Korea.
² Department of Rehabilitation Medicine, Kangdong Sacred Heart Hospital, College of Medicine Hallym University, 150 Seongan-ro, Gangdong-gu, Seoul, 05355, South Korea.
³ Department of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine Hallym University, 94-200 Yeong-deungpo-Dong, Yeongdeungpo-Ku, Seoul, 07247, South Korea.
⁴ Department of Pediatrics, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, 94-200 Yeong-deungpo-Dong, Yeongdeungpo-Ku, Seoul, 07247, South Korea.
⁵ Department of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine Hallym University, 94-200 Yeong-deungpo-Dong, Yeongdeungpo-Ku, Seoul, 07247, South Korea. Electronic address: pmrseo@hallym.or.kr.

PMID: 35430216
DOI: 10.1016/j.abb.2022.109215

Abstract

Post-burn hypertrophic scars are characterized by excessive accumulation of extracellular matrix secreted by fibroblasts. Exosomes are membrane lipid extracellular vesicles that play a pivotal role in cellular communication. Previous studies revealed the role of stem cell-derived exosomes in repairing damaged tissues, and also showed that cancer cell-derived exosomes could affect the disease pathogenesis. However, the functional properties of exosomes derived from hypertrophic scar fibroblasts (HTSFs) have not yet been studied extensively. In this study, we aimed to investigate whether HTSFs-derived exosomes can change the fibrosis-related signaling pathways in human normal fibroblasts (HNFs). HTSFs and HNFs were isolated from human hypertrophic scar tissues. HTSFs-derived exosomes were extracted and treated to HNFs. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect mRNA and protein expression, respectively, and cell proliferation and mobility were also assessed. Exosome treatment markedly increased cell proliferation and migration, and induced small mother against decapentaplegic (SMAD) signaling by increasing the levels of phosphorylated SMAD2 and SMAD1/5/8. The levels of TAK1 signaling components were also increased after exosome treatment to HNFs, including phosphorylated TAK1, p38, ERK, and JNK. HTSFs-derived exosomes further induced the epithelial-mesenchymal transition by decreasing the expression level of E-cadherin and increasing the expression levels of N-cadherin and vimentin. Consequently, the expression levels of fibronectin, type Ⅰ collagen, and type Ⅲ collagen were increased. Our results demonstrate the fibrotic property of HTSFs-derived exosomes, which suggests a potential functional role in hypertrophic scar development and a new therapeutic target.

Keywords: Exosome; Fibroblast; Hypertrophic scar; SMAD signaling; TAK1 signaling.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cells, Cultured
Cicatrix, Hypertrophic* / metabolism
Exosomes* / metabolism
Fibroblasts / metabolism
Fibrosis
Humans
Signal Transduction