title: Treatment with cytokine thymic stromal lymphopoietin short hairpin RNA substantially reduces TGF-β1-induced interstitial cellular fibrosis.
abstract: Thymic stromal lymphopoietin (TSLP) has previously been linked to allergic inflammatory diseases, and tissue fibrosis and organ dysfunction may also arise from such inflammation. It remains unclear, however, whether TSLP plays any role in the occurrence of renal fibrosis, so this study investigated that possibility. An in vitro fibrosis model was established by treating normal rat kidney fibroblast (NRK-49F) cells with transforming growth factor-β1 (TGF-β1), after which the levels of various fibrogenic markers (e.g., fibronectin) and downstream fibrogenic signal proteins (e.g., smad 7) were investigated. Also, TSLP shRNA was used to silence the effects of TSLP, while an ELISA was conducted to evaluate the fibronectin secretions. The level of fibronectin in the NRK-49F cells was dose- and time-dependently increased by the administration of exogenous TSLP (P<0.05). TSLP also significantly increased the level of fibrosis signaling, in addition to inducing a marked decrease in the down-regulation of Smad7. Interestingly, the application of TSLP shRNA caused a stark reversal of the TGF-β1-induced cellular fibrosis while simultaneously leading to the suppression of fibronectin and fibrogenic signal proteins. Taken together, these observations provide insights into how extracellular matrices develop and could thus lead to potential therapeutic interventions for the suppression of renal fibrosis.
authors: Graduate Institute of Biomedical Science, National Sun Yat-sen University, Kaohsiung, Taiwan; Graduate Institute of Medical Laboratory Science and Biotechnology, Chung Hwa Medical University, Tainan, Taiwan.
authors: Pei-Fang
authors: PF
authors: Hsieh
authors: Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan.
authors: Shu-Fen
authors: SF
authors: Liu
authors: Graduate Institute of Biomedical Science, Chung Hwa Medical University, Tainan, Taiwan.
authors: Tsung-Jen
authors: TJ
authors: Hung
authors: Department of Food nutrition, Chung Hwa Medical University, Tainan, Taiwan.
authors: Chien-Ya
authors: CY
authors: Hung
authors: Graduate Institute of Medical Laboratory Science and Biotechnology, Chung Hwa Medical University, Tainan, Taiwan.
authors: Guo-Zheng
authors: GZ
authors: Liu
authors: Department of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Lea-Yea
authors: LY
authors: Chuang
authors: Department of Acupressure Technology, Chung Hwa Medical University, Tainan, Taiwan.
authors: Mei-Fen
authors: MF
authors: Chen
authors: Department of Physical Medicine and Rehabilitation, Kaohsiung Veterans General Hospital, Taiwan.
authors: Jue-Long
authors: JL
authors: Wang
authors: Graduate Institute of Medical Laboratory Science and Biotechnology, Chung Hwa Medical University, Tainan, Taiwan; Department of Medical Technology, Kaohsiung Veterans General Hospital Tainan Branch, Tainan, Taiwan.
authors: Ming-Der
authors: MD
authors: Shi
authors: Department of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan; Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Chen Hung
authors: CH
authors: Hsu
authors: Graduate Institute of Biomedical Science, National Sun Yat-sen University, Kaohsiung, Taiwan. Electronic address: shiue.shirley@gmail.com.
authors: Yow-Ling
authors: YL
authors: Shiue
authors: Graduate Institute of Medical Laboratory Science and Biotechnology, Chung Hwa Medical University, Tainan, Taiwan. Electronic address: Call0955443221@gmail.com.
authors: Yu-Lin
authors: YL
authors: Yang
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D008954:Models, Biological; D034741:RNA, Small Interfering / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D005353:Fibronectins; D034741:RNA, Small Interfering; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D000094632:Thymic Stromal Lymphopoietin; C000721968:TSLP protein, rat
keywords: Fibrosis; NRK49F; TSLP