1. Academic Validation
  2. TSLP-induced collagen type-I synthesis through STAT3 and PRMT1 is sensitive to calcitriol in human lung fibroblasts

TSLP-induced collagen type-I synthesis through STAT3 and PRMT1 is sensitive to calcitriol in human lung fibroblasts

  • Biochim Biophys Acta Mol Cell Res. 2021 Sep;1868(10):119083. doi: 10.1016/j.bbamcr.2021.119083.
Ai Jin 1 Xuemei Tang 1 Weiqi Zhai 1 Yuwen Li 1 Qingzhu Sun 2 Li Liu 3 Xiaojun Yang 1 Hui Ren 4 Shemin Lu 5
Affiliations

Affiliations

  • 1 College of Animal Science and Technology, Northwest A&F University, Yangling 712100, Shaanxi, PR China.
  • 2 College of Animal Science and Technology, Northwest A&F University, Yangling 712100, Shaanxi, PR China. Electronic address: sunqingzhu@nwafu.edu.cn.
  • 3 Department of Basic Medical Science, Xi'an Medical College, Xi'an, Shaanxi 710021, PR China. Electronic address: lazurite89@126.com.
  • 4 Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
  • 5 Department of Biochemistry and Molecular Biology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China.
Abstract

Airway wall remodeling, a main pathology of asthma was linked to vitamin-D deficiency and protein arginine methyltransferase-1 (PRMT1) expression in sub-epithelial cell layers. Calcitriol reduced remodeling in asthma model, but its mode of action is unclear. This study assessed the effect of calcitriol on PRMT1-dependent fibroblast remodeling in human lung fibroblasts, and allergen-induced asthma in E3-rats. Fibroblasts were activated with thymic stromal lymphopoietin (TLSP); asthma was induced by ovalbumin inhalation in rats. The airway structure was assessed by immunohistology. Protein expression in fibroblasts and activation of the mitogen activated protein kinases were detected by Western-blotting. Transcription factor activation was determined by luciferase reporter assay. PRMT1 action was blocked by siRNA and PRMT-inhibition. Ovalbumin upregulated the expression of TSLP, PRMT1, matrix metallopro-teinase-1 (MMP1), interleukin-25, and collagen type-I in sub-epithelial fibroblasts. In isolated fibroblasts, TSLP induced the same proteins, which were blocked by inhibition of ERK1/2 and p38. TLSP induced PRMT1 through activation of signal transducer and activator of transcription-3. PRMT1 inhibition reduced collagen type-I expression and suppressed MMP1. In fibroblasts, calcitriol supplementation over 12 days prevented TSLP-induced remodeling by blocking the PRMT1 levels. Interestingly, short-term calcitriol treatment had no such effect. The data support the beneficial role of calcitriol in asthma therapy.

Keywords

Airway remodeling; Calcitriol; Collagen type-I; Mitogen activated protein kinases; Protein arginine methyltransferase-1; Thymic stromal-lymphopoietin.

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