Cyclophilin A/CD147 signaling induces the epithelial-to-mesenchymal transition and renal fibrosis in chronic allograft dysfunction by regulating p38 MAPK signaling
Objective Our study was designed to explore the role of Cyclophilin A (CyPA)/CD147 signaling in renal allograft fibrosis and chronic allograft dysfunction (CAD).Materials and methods A rat renal transplant model with significant CAD was successfully achieved. Renal allograft tissues and blood sample...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2022-12-01
|
| Series: | Renal Failure |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2022.2126788 |
| _version_ | 1811227049623289856 |
|---|---|
| author | Xuzhong Liu Zhiwang Tang Xi Jiang Tianwei Wang Lun Zhao Zongyuan Xu Kun Liu |
| author_facet | Xuzhong Liu Zhiwang Tang Xi Jiang Tianwei Wang Lun Zhao Zongyuan Xu Kun Liu |
| author_sort | Xuzhong Liu |
| collection | DOAJ |
| description | Objective Our study was designed to explore the role of Cyclophilin A (CyPA)/CD147 signaling in renal allograft fibrosis and chronic allograft dysfunction (CAD).Materials and methods A rat renal transplant model with significant CAD was successfully achieved. Renal allograft tissues and blood samples were collected. Hematoxylin and eosin, Masson’s, and immunohistochemistry staining were performed. Since CD147 is mainly expressed in the renal tubular epithelial cells, human HK-2 cells were used and intervened by specific concentrations of CyPA, and the total protein and mRNA were extracted. Western blot assay and polymerase chain reaction were performed to explore the protein and mRNA expression of CyPA, CD147, and epithelial-to-mesenchymal transition (EMT)-related biomarkers. SiRNA-CD147 and specific inhibitors of p38 MAPK were used to explore the cellular mechanisms involved in the process.Results We have successfully established and validated a 20-week renal transplant CAD model. We observed significant distributed and expressed CyPA and CD147 in the renal allograft fibrotic tissues. We also found a significant expression of CD147 and EMT-related markers in the HK-2 cells stimulated by CyPA. The CD147 siRNA confirmed the previous in vitro results. The selective inhibition of MAPK suggested the notable role of p38 MAPK signaling pathway in the CyP/CD147 signaling involved in renal allograft fibrosis.Conclusions Our study reported the positive relationship of CyPA-CD147 signaling with renal allograft dysfunction. The in vitro study suggested that CyPA-CD147 signaling induce the development of the EMT process by p38 MAPK signaling, thus contributing to renal allograft fibrosis and CAD. |
| first_indexed | 2024-04-12T09:34:39Z |
| format | Article |
| id | doaj.art-af13c81d074a4eab8e6414a258382979 |
| institution | Directory Open Access Journal |
| issn | 0886-022X 1525-6049 |
| language | English |
| last_indexed | 2024-04-12T09:34:39Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj.art-af13c81d074a4eab8e6414a2583829792022-12-22T03:38:15ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492022-12-014411585159410.1080/0886022X.2022.2126788Cyclophilin A/CD147 signaling induces the epithelial-to-mesenchymal transition and renal fibrosis in chronic allograft dysfunction by regulating p38 MAPK signalingXuzhong Liu0Zhiwang Tang1Xi Jiang2Tianwei Wang3Lun Zhao4Zongyuan Xu5Kun Liu6Department of Urology, Huai’an First People’s Hospital, Nanjing Medical University, Nanjing, Huai’an, ChinaDepartment of Urology, Huai’an First People’s Hospital, Nanjing Medical University, Nanjing, Huai’an, ChinaDepartment of Urology, Huai’an First People’s Hospital, Nanjing Medical University, Nanjing, Huai’an, ChinaDepartment of Urology, Huai’an First People’s Hospital, Nanjing Medical University, Nanjing, Huai’an, ChinaDepartment of Urology, Huai’an First People’s Hospital, Nanjing Medical University, Nanjing, Huai’an, ChinaDepartment of Urology, Huai’an First People’s Hospital, Nanjing Medical University, Nanjing, Huai’an, ChinaDepartment of Urology, Huai’an First People’s Hospital, Nanjing Medical University, Nanjing, Huai’an, ChinaObjective Our study was designed to explore the role of Cyclophilin A (CyPA)/CD147 signaling in renal allograft fibrosis and chronic allograft dysfunction (CAD).Materials and methods A rat renal transplant model with significant CAD was successfully achieved. Renal allograft tissues and blood samples were collected. Hematoxylin and eosin, Masson’s, and immunohistochemistry staining were performed. Since CD147 is mainly expressed in the renal tubular epithelial cells, human HK-2 cells were used and intervened by specific concentrations of CyPA, and the total protein and mRNA were extracted. Western blot assay and polymerase chain reaction were performed to explore the protein and mRNA expression of CyPA, CD147, and epithelial-to-mesenchymal transition (EMT)-related biomarkers. SiRNA-CD147 and specific inhibitors of p38 MAPK were used to explore the cellular mechanisms involved in the process.Results We have successfully established and validated a 20-week renal transplant CAD model. We observed significant distributed and expressed CyPA and CD147 in the renal allograft fibrotic tissues. We also found a significant expression of CD147 and EMT-related markers in the HK-2 cells stimulated by CyPA. The CD147 siRNA confirmed the previous in vitro results. The selective inhibition of MAPK suggested the notable role of p38 MAPK signaling pathway in the CyP/CD147 signaling involved in renal allograft fibrosis.Conclusions Our study reported the positive relationship of CyPA-CD147 signaling with renal allograft dysfunction. The in vitro study suggested that CyPA-CD147 signaling induce the development of the EMT process by p38 MAPK signaling, thus contributing to renal allograft fibrosis and CAD.https://www.tandfonline.com/doi/10.1080/0886022X.2022.2126788Cyclophilin ACD147epithelial-to-mesenchymal transitionkidney transplantationchronic allograft dysfunction |
| spellingShingle | Xuzhong Liu Zhiwang Tang Xi Jiang Tianwei Wang Lun Zhao Zongyuan Xu Kun Liu Cyclophilin A/CD147 signaling induces the epithelial-to-mesenchymal transition and renal fibrosis in chronic allograft dysfunction by regulating p38 MAPK signaling Renal Failure Cyclophilin A CD147 epithelial-to-mesenchymal transition kidney transplantation chronic allograft dysfunction |
| title | Cyclophilin A/CD147 signaling induces the epithelial-to-mesenchymal transition and renal fibrosis in chronic allograft dysfunction by regulating p38 MAPK signaling |
| title_full | Cyclophilin A/CD147 signaling induces the epithelial-to-mesenchymal transition and renal fibrosis in chronic allograft dysfunction by regulating p38 MAPK signaling |
| title_fullStr | Cyclophilin A/CD147 signaling induces the epithelial-to-mesenchymal transition and renal fibrosis in chronic allograft dysfunction by regulating p38 MAPK signaling |
| title_full_unstemmed | Cyclophilin A/CD147 signaling induces the epithelial-to-mesenchymal transition and renal fibrosis in chronic allograft dysfunction by regulating p38 MAPK signaling |
| title_short | Cyclophilin A/CD147 signaling induces the epithelial-to-mesenchymal transition and renal fibrosis in chronic allograft dysfunction by regulating p38 MAPK signaling |
| title_sort | cyclophilin a cd147 signaling induces the epithelial to mesenchymal transition and renal fibrosis in chronic allograft dysfunction by regulating p38 mapk signaling |
| topic | Cyclophilin A CD147 epithelial-to-mesenchymal transition kidney transplantation chronic allograft dysfunction |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2022.2126788 |
| work_keys_str_mv | AT xuzhongliu cyclophilinacd147signalinginducestheepithelialtomesenchymaltransitionandrenalfibrosisinchronicallograftdysfunctionbyregulatingp38mapksignaling AT zhiwangtang cyclophilinacd147signalinginducestheepithelialtomesenchymaltransitionandrenalfibrosisinchronicallograftdysfunctionbyregulatingp38mapksignaling AT xijiang cyclophilinacd147signalinginducestheepithelialtomesenchymaltransitionandrenalfibrosisinchronicallograftdysfunctionbyregulatingp38mapksignaling AT tianweiwang cyclophilinacd147signalinginducestheepithelialtomesenchymaltransitionandrenalfibrosisinchronicallograftdysfunctionbyregulatingp38mapksignaling AT lunzhao cyclophilinacd147signalinginducestheepithelialtomesenchymaltransitionandrenalfibrosisinchronicallograftdysfunctionbyregulatingp38mapksignaling AT zongyuanxu cyclophilinacd147signalinginducestheepithelialtomesenchymaltransitionandrenalfibrosisinchronicallograftdysfunctionbyregulatingp38mapksignaling AT kunliu cyclophilinacd147signalinginducestheepithelialtomesenchymaltransitionandrenalfibrosisinchronicallograftdysfunctionbyregulatingp38mapksignaling |