1. Academic Validation
  2. LAMB3 Promotes Myofibrogenesis and Cytoskeletal Reorganization in Endometrial Stromal Cells via the RhoA/ROCK1/MYL9 Pathway

LAMB3 Promotes Myofibrogenesis and Cytoskeletal Reorganization in Endometrial Stromal Cells via the RhoA/ROCK1/MYL9 Pathway

  • Cell Biochem Biophys. 2023 Oct 6. doi: 10.1007/s12013-023-01186-5.
Xiaomei Qin # 1 Bin Zeng # 2 Suren R Sooranna 3 4 Mujun Li 5
Affiliations

Affiliations

  • 1 Gynecology Section, Department of Obstetrics and Gynecology, The First Affiliated Hospital, Guangxi Medical University, 530000, Nanning, China.
  • 2 Reproductive Medical Center, The First Affiliated Hospital, Guangxi Medical University, 530000, Nanning, China.
  • 3 Department of Metabolism, Digestion and Reproduction Faculty of Medicine Imperial College London Chelsea & Westminster Hospital, London, SW10 9NH, UK.
  • 4 Life Science and Clinical Research Center, Youjiang Medical University for Nationalities, Baise, China.
  • 5 Reproductive Medical Center, The First Affiliated Hospital, Guangxi Medical University, 530000, Nanning, China. lmj1699@sr.gxmu.edu.cn.
  • # Contributed equally.
Abstract

LAMB3, a major extracellular matrix and basal membrane component, is involved in wound healing. We aimed to understand its role in Asherman's syndrome (AS), which is associated with infertility, by using bioinformatics analysis and cultured endometrial stromal cells (ESCs). MRNAs extracted from tissues obtained from control subjects and patients with severe intrauterine adhesion were sequenced and subjected to bioinformatics analysis and the RhoA/ROCK1/MYL9 pathway was implicated and this subsequently studied using cultured primary ESCs. The effects of overexpression and knockdown and activation and inhibition of LAMB3 on the mesenchymal to myofibroblastic phenotypic transformation of ECCs were assessed using PCR and western blot analysis. Phalloidin was used to localize the actin cytoskeletal proteins. Silencing of LAMB3 reversed the TGF-β-induced ESC myofibroblast phenotype conversion, whereas overexpression of LAMB3 promoted this process. Activation and silencing of LAMB3 led to remodeling of the ESC Cytoskeleton. Overexpression and silencing of LAMB3 caused activation and inhibition of ESCs, respectively. Y-27632 and LPA reversed the activation and inhibition of the RhoA/ROCK1/MYL9 pathway after overexpression and silencing, respectively. These results suggest that LAMB3 can regulate ESC fibrosis transformation and Cytoskeleton remodeling via the RhoA/ROCK1/MYL9 pathway. This study provides a potential new target for gene therapy and drug intervention of AS.

Keywords

Asherman’s syndrome; Cytoskeletal Reorganization; LAMB3; Myofibrogenesis; RhoA/ROCK1/MYL9.

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