Hapln1 promotes dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping

被引：1

作者：

Hao, Ding-Jun ^{[1
]}

Qin, Yue ^{[2
]}

Zhou, Shi-Jie ^{[4
]}

Dong, Bu-Huai ^{[2
]}

Yang, Jun-Song ^{[1
]}

Zou, Peng ^{[1
]}

Wang, Li-Ping ^{[3
]}

Zhao, Yuan-Ting ^{[1
]}

机构：

[1] Xi An Jiao Tong Univ, Honghui Hosp, Dept Spine Surg, Xian 710054, Peoples R China

[2] Xi An Jiao Tong Univ, Honghui Hosp, Dept Anesthesiol, Xian 710054, Peoples R China

[3] Xi An Jiao Tong Univ, Honghui Hosp, Dept Cardiovasc Med, Xian 710054, Peoples R China

[4] Sichuan Univ, West China Hosp, Collaborat Innovat Ctr Biotherapy, State Key Lab Biotherapy, Chengdu 610041, Peoples R China

来源：

JOURNAL OF PHARMACEUTICAL ANALYSIS | 2024年 / 14卷 / 03期

关键词：

Hapln1; Versican; GDF11; iPSC-CMs; Cardiomyocyte proliferation; HEART; DIFFERENTIATION; PROTEOGLYCAN; MATURATION; BINDING;

D O I：

10.1016/j.jpha.2023.09.013

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Hyaluronan and proteoglycan link protein 1 (Hapln1) supports active cardiomyogenesis in zebra fish hearts, but its regulation in mammal cardiomyocytes is unclear. This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) and an adult mouse model of myocardial infarction. HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models, respectively. Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration. The results showed that recombinant human Hapln1 (rhHapln1) promotes the proliferation of hiPSC-CMs in a dose-dependent manner. As a physical binding protein of Hapln1, versican interacted with Nodal growth differentiation factor (NODAL) and growth differentiation factor 11 (GDF11). GDF11, but not NODAL, was expressed by hiPSC-CMs. GDF11 expression was unaffected by rhHapln1 treatment. However, this molecule was required for rhHapln1-mediated activation of the transforming growth factor (TGF)- B/Drosophila mothers against decapentaplegic protein (SMAD)2/3 signaling in hiPSC-CMs, which stimulates cell dedifferentiation and proliferation. Recombinant mouse Hapln1 (rmHapln1) could induce cardiac regeneration in the adult mouse model of myocardial infarction. In addition, rmHapln1 induced hiPSC-CM proliferation. In conclusion, Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF- B/SMAD2/3 signaling pathway. Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a potential reagent for repairing damaged hearts. (c) 2023 The Authors. Published by Elsevier B.V. on behalf of Xi 'an Jiaotong University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页码：335 / 347

页数：13