Phosphorylated vimentin at Ser72 is associated with epithelial–mesenchymal transition in lupus nephritis

Author:

Wang Daji1ORCID,Zhang Fan2,He Jing23,Li Chuyi4,Liu Xingjiao3,Zhang Meng5,Huang Haihui5,Xiong Zuying2,Duan Hongxia4,Huang Xiaoyan2,Wang Meiying36ORCID

Affiliation:

1. Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen China

2. Department of Nephrology Peking University Shenzhen Hospital Shenzhen China

3. Department of Rheumatology and Immunology, Shenzhen Second People's Hospital The First Affiliated Hospital of Shenzhen University Shenzhen China

4. Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics Chinese Academy of Sciences Beijing China

5. Department of Pathology Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Shenzhen China

6. Department of Rheumatology and Immunology Peking University Shenzhen Hospital Shenzhen China

Abstract

AbstractObjectivesTo measure the expression of vimentin and its phosphorylated forms in lupus nephritis (LN) and explore their potential role in LN development.MethodsLupus renal biopsies from LN patients and normal renal biopsies from kidney transplant donors were collected. The expression of vimentin and its phosphorylated forms (p‐vimentin (Ser39, Ser56, Ser72, Ser83, and Tyr117)) were measured by Western blots and immunohistochemistry. To construct stable cell line that overexpress vimentin and its phosphorylated forms, an immortalized proximal tubule epithelial cell line (HK‐2 cells) was utilized. The roles of vimentin and its phosphorylated forms on the migration of HK‐2 cells were examined by transwell migration assay and wound healing analysis.ResultsWe first observed a significant upregulation of vimentin protein in TGFβ1‐induced HK‐2 cells. This finding was further confirmed in renal tissues obtained from LN patients and animal model. Interestingly, among the five phosphorylated forms of vimentin, only vimentin phosphorylated at Ser72 was upregulated in LN. Through the establishment of stable vimentin and its phosphorylated forms overexpression in HK‐2 cells, we found that the overexpression of vimentin and its phosphorylated forms at Ser72 significantly enhances the cell migration.ConclusionsVimentin phosphorylated on Ser72 is important for renal epithelial cell migration, which would enhance the progression of vimentin‐induced epithelial–mesenchymal transition during LN development.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Guangdong Province

Publisher

Wiley

Subject

Rheumatology

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