Effect of WTAP on collagen deposition in bleomycin-induced pulmonary fibrosis

Acta Universitatis Medicinalis Anhui     font:big middle small

Found programs: Natural Science Research Project of Anhui Educational Committee (No . 2023AH040376) Corresponding author Chen Qi , E-mail : 1228022438@ qq . com

Authors:Zhang Yunsen1 , 2 , Liu Zhenyu1 , 2 , Liu Zhiyan1 , 2 , Lin Lichan1 , 2 , Sha Jiming3 , Tao Hui 1 , 2 , Chen Qi 1 , 2

Keywords:Wilms ′tumor 1-associated protein; pulmonary fibrosis; bleomycin; epitranscriptome; collagen; N6 - methyladenosine

DOI:10.19405/j.cnki.issn1000-1492.2025.02.011

〔Abstract〕 Abstract Objective To explore the effect of Wilms ′tumor 1-associated protein (WTAP) on tissue collagen dep- osition in pulmonary fibrosis caused by bleomycin . Methods 60 mice were randomly divided into four groups : control group ( Control group) , Bleomycin-induced pulmonary fibrosis group ( BLM group) , pulmonary fibrosis lentivirus empty vector control group ( BLM + LV-NC group) , pulmonary fibrosis WTAP lentivirus group virus group (BLM + LV-WTAP group) . Experimental pulmonary fibrosis mouse model was established by subcutaneous injection of bleomycin (35 mg/kg) into the abdomen , twice a week for a total of 8 times . After modeling , Western Blot was used to detect the protein expression of fibrosis-related markers α-smooth muscle actin ( α-SMA) , type I collagen (Collagen Ⅰ ) , fibronectin (Fibronectin) , and WTAP protein . Masson staining and Sirius Red staining were used to detect collagen deposition . RT-qPCR was used to detect WTAP mRNA expression , WTAP lentivirus infection effect , and Collagen Ⅰ mRNA expression . Results Compared with the Control group , the expression of pulmonary fibrosis markers α-SMA (P < 0. 001) , Collagen Ⅰ (P < 0. 001) , and Fibronectin (P < 0. 01) protein in the BLM group all increased . Masson staining (P < 0. 001) and Sirius Red staining (P < 0. 001) confirmed that significant collagen deposition occurred in the lung tissue of the BLM group . In addition , the expression of WTAP protein in the lung tissue of the BLM group increased (P < 0. 01) . Compared with the Control group , the expres- sion of WTAP mRNA in the BLM group increased (P < 0. 001) . Compared with the BLM + LV-NC group , the ex- pression of WTAP mRNA in the tissues of the BLM + LV-WTAP group decreased (P < 0. 001) , proving that virus infection is effective . After infection with WTAP lentivirus , collagen fiber deposition decreased (P < 0. 001) , Col- lagen Ⅰ mRNA (P < 0. 001) level decreased , and protein (P < 0. 001) expression decreased in the BLM + LV- WTAP group . Conclusion Knocking down of WTAP can reduce collagen deposition in bleomycin-induced pulmo- nary fibrosis tissue in mice and improve experimental pulmonary fibrosis .