Vaccination against connective tissue growth factor attenuates the development of renal fibrosis
Abstract There is a critical need for efficient treatment of chronic kidney disease (CKD). Renal fibrosis is a final common pathway to end-stage renal disease independent of the underlying etiology, and connective tissue growth factor (CTGF) is a well-recognized profibrotic factor in fibrosis of var...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-15118-5 |
| _version_ | 1817976662664413184 |
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| author | Takashin Nakayama Tatsuhiko Azegami Kaori Hayashi Akihito Hishikawa Norifumi Yoshimoto Ran Nakamichi Erina Sugita Hiroshi Itoh |
| author_facet | Takashin Nakayama Tatsuhiko Azegami Kaori Hayashi Akihito Hishikawa Norifumi Yoshimoto Ran Nakamichi Erina Sugita Hiroshi Itoh |
| author_sort | Takashin Nakayama |
| collection | DOAJ |
| description | Abstract There is a critical need for efficient treatment of chronic kidney disease (CKD). Renal fibrosis is a final common pathway to end-stage renal disease independent of the underlying etiology, and connective tissue growth factor (CTGF) is a well-recognized profibrotic factor in fibrosis of various organ systems. Here, we developed a novel peptide vaccine against CTGF to attenuate the development of renal fibrosis. Three inoculations with this CTGF vaccine at 2-week intervals elicited antibodies specifically binding to human full-length CTGF, and the antigen-specific serum IgG antibody titers were maintained for > 30 weeks. The efficacy of the CTGF vaccine on renal fibrosis was evaluated in adenine-induced CKD and unilateral ureteral obstruction (UUO) murine models. In adenine-induced CKD model, immunization with the CTGF vaccine attenuated renal interstitial fibrosis. Vaccinated mice showed low levels of serum creatinine and urea nitrogen and low urine albumin–creatinine ratio compared with vehicle-treated mice. In UUO model, the CTGF vaccination also suppressed the onset of renal fibrosis. In an in vitro study, CTGF vaccine-elicited IgG antibodies efficiently suppressed CTGF-induced- and transforming growth factor-β-induced α-smooth muscle actin expression in kidney fibroblasts. These results demonstrate that the CTGF vaccine is a promising strategy to attenuate the development of renal fibrosis. |
| first_indexed | 2024-04-13T22:05:39Z |
| format | Article |
| id | doaj.art-d5e6a67523ac448b987f60a8d96d5921 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T22:05:39Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d5e6a67523ac448b987f60a8d96d59212022-12-22T02:27:57ZengNature PortfolioScientific Reports2045-23222022-06-0112111310.1038/s41598-022-15118-5Vaccination against connective tissue growth factor attenuates the development of renal fibrosisTakashin Nakayama0Tatsuhiko Azegami1Kaori Hayashi2Akihito Hishikawa3Norifumi Yoshimoto4Ran Nakamichi5Erina Sugita6Hiroshi Itoh7Department of Internal Medicine, Keio University School of MedicineDepartment of Internal Medicine, Keio University School of MedicineDepartment of Internal Medicine, Keio University School of MedicineDepartment of Internal Medicine, Keio University School of MedicineDepartment of Internal Medicine, Keio University School of MedicineDepartment of Internal Medicine, Keio University School of MedicineDepartment of Internal Medicine, Keio University School of MedicineDepartment of Internal Medicine, Keio University School of MedicineAbstract There is a critical need for efficient treatment of chronic kidney disease (CKD). Renal fibrosis is a final common pathway to end-stage renal disease independent of the underlying etiology, and connective tissue growth factor (CTGF) is a well-recognized profibrotic factor in fibrosis of various organ systems. Here, we developed a novel peptide vaccine against CTGF to attenuate the development of renal fibrosis. Three inoculations with this CTGF vaccine at 2-week intervals elicited antibodies specifically binding to human full-length CTGF, and the antigen-specific serum IgG antibody titers were maintained for > 30 weeks. The efficacy of the CTGF vaccine on renal fibrosis was evaluated in adenine-induced CKD and unilateral ureteral obstruction (UUO) murine models. In adenine-induced CKD model, immunization with the CTGF vaccine attenuated renal interstitial fibrosis. Vaccinated mice showed low levels of serum creatinine and urea nitrogen and low urine albumin–creatinine ratio compared with vehicle-treated mice. In UUO model, the CTGF vaccination also suppressed the onset of renal fibrosis. In an in vitro study, CTGF vaccine-elicited IgG antibodies efficiently suppressed CTGF-induced- and transforming growth factor-β-induced α-smooth muscle actin expression in kidney fibroblasts. These results demonstrate that the CTGF vaccine is a promising strategy to attenuate the development of renal fibrosis.https://doi.org/10.1038/s41598-022-15118-5 |
| spellingShingle | Takashin Nakayama Tatsuhiko Azegami Kaori Hayashi Akihito Hishikawa Norifumi Yoshimoto Ran Nakamichi Erina Sugita Hiroshi Itoh Vaccination against connective tissue growth factor attenuates the development of renal fibrosis Scientific Reports |
| title | Vaccination against connective tissue growth factor attenuates the development of renal fibrosis |
| title_full | Vaccination against connective tissue growth factor attenuates the development of renal fibrosis |
| title_fullStr | Vaccination against connective tissue growth factor attenuates the development of renal fibrosis |
| title_full_unstemmed | Vaccination against connective tissue growth factor attenuates the development of renal fibrosis |
| title_short | Vaccination against connective tissue growth factor attenuates the development of renal fibrosis |
| title_sort | vaccination against connective tissue growth factor attenuates the development of renal fibrosis |
| url | https://doi.org/10.1038/s41598-022-15118-5 |
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