热休克蛋白B-1在心肌损伤中的表达变化及其对TGF-β1成熟过程的调控作用

doi:10.3969/j.issn.1006-5725.2026.14.001

Abstract

Abstract:

Objective To investigate the expression changes of heat shock protein beta-1 （HSPB1） during myocardial injury and its regulatory role in the maturation process of transforming growth factor-β1 （TGF-β1）. Methods Publicly accessible cardiac single-cell transcriptomic datasets， an isoproterenol （ISO）-induced mouse myocardial injury model， and H9c2 cell experiments were integrated to evaluate the expression changes of HSPB1. The overexpression of HSPB1 and the Cys137 mutation were employed to assess their impacts on pro-TGF-β1， mature TGF-β1， and the Smad signaling pathway. Molecular docking and bidirectional co-immunoprecipitation （Co-IP） assays were carried out to analyze the interaction between HSPB1 and pro-TGF-β1. Results Public cardiac single-cell transcriptomic data have demonstrated that HSPB1 is expressed in multiple cardiac cell populations， with relatively higher expression levels in cardiomyocytes. In comparison with the control group， ISO treatment led to a reduction in the left ventricular ejection fraction （LVEF） in mice from （95.20 ± 2.82）% to （82.28 ± 3.05）% and （63.18 ± 4.20）%， as well as a decrease in the left ventricular fractional shortening （LVFS） from （69.45 ± 8.32）% to （48.66 ± 3.16）% and （38.32 ± 2.23）% （all P < 0.001）. This was accompanied by aggravated myocardial fibrosis and cardiomyocyte hypertrophy. Immunohistochemistry and Western blot analyses indicated that HSPB1 expression was significantly up-regulated in myocardial tissue after 14 days of ISO treatment （P = 0.000 4 and P < 0.000 1， respectively）. H9c2 cell experiments revealed that， under ISO stimulation， overexpression of wild-type HSPB1 （HSPB1-WT） increased pro-TGF-β1 levels， while reducing the mature TGF-β1/pro-TGF-β1 ratio， partially decreasing mature TGF-β1 levels， and lowering p-Smad2/3 levels （vs. ISO group， P = 0.037 5， 0.049 9， and 0.002 1， respectively）. These effects were markedly attenuated in the Cys137 mutant， with related indicators significantly elevated compared with the HSPB1-WT group （P = 0.000 1， 0.001 8， and 0.000 6， respectively）. Molecular docking analysis suggested a potential interaction interface between HSPB1 and pro-TGF-β1. Bidirectional Co-IP further confirmed the interaction between the two proteins， whereas the Cys137 mutation weakened their binding signal. Conclusions HSPB1 may interact with pro-TGF-β1 via its redox-sensitive residue Cys137 and participate in restricting its excessive maturation process， thus modulating the TGF-β1/Smad signaling activity. This study offers a novel molecular perspective for comprehending the fine-tuned regulation of myocardial fibrosis-related signaling pathways.

Key words: heat shock protein beta-1, transforming growth factor-β1, conformational stability, cardiac fibrosis

CLC Number:

R542.2⁺3

Daqing DENG,Juan ZHOU,Jia WANG,Yiqun LIU,Keqin CHEN,Lin ZHOU,Xiehong LIU. Expression changes of heat shock protein B-1 in myocardial injury and its regulatory effect on the maturation process of TGF-β1[J]. The Journal of Practical Medicine, 2026, 42(14): 2477-2487.

Figures/Tables 7

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构建体	位点	氨基酸变化	关键序列（5'→3'）
HSPB1-WT	Cys137	Cys → -	ATC TCC CGG TGC TTC ACG CGG
HSPB1-C137S	Ser137	Cys → Ser	ATC TCC CGG AGC TTC ACG CGG

Expression changes of heat shock protein B-1 in myocardial injury and its regulatory effect on the maturation process of TGF-β1

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