GOLPH3 promotes calcium oxalate-induced renal injury and fibrosis through Golgi stress-mediated apoptosis and inflammatory responses
Abstract A common urological disorder, calcium oxalate (CaOx) stones are the most common form of kidney stones. Deposition of CaOx crystals leads to tubular damage, interstitial fibrosis, and chronic kidney disease. Understanding the intrinsic mechanisms of kidney stone formation is essential for th...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-03-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-91638-0 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850252123089928192 |
|---|---|
| author | Bao-feng Song Bo-jun Li Yushi Sun Ming Li Ting Rao Yuan Ruan Fan Cheng |
| author_facet | Bao-feng Song Bo-jun Li Yushi Sun Ming Li Ting Rao Yuan Ruan Fan Cheng |
| author_sort | Bao-feng Song |
| collection | DOAJ |
| description | Abstract A common urological disorder, calcium oxalate (CaOx) stones are the most common form of kidney stones. Deposition of CaOx crystals leads to tubular damage, interstitial fibrosis, and chronic kidney disease. Understanding the intrinsic mechanisms of kidney stone formation is essential for the prevention of kidney stones and the development of new therapeutic agents. The Golgi apparatus is a key organelle in the secretory pathway of eukaryotic cells, which plays an important role in the sorting, modification, and transport of proteins within the cell, and has been reported to be involved in several diseases, including prostate tumors, gastrointestinal tumors, sepsis, and so on. GOLPH3 is also known as GPP34, GMx33, or MIDAS. It is a glycoprotein that regulates traffic between the trans-Golgi network and the cell membrane. However, its role in renal injury caused by CaOx crystal deposition is still unclear. Results from immunohistochemistry, qRT-PCR, western blot, and public database single nucleotide RNA-seq showed that GOLPH3 was significantly upregulated in kidney stone patients and animal kidneys. Significant inhibition of Golgi stress, apoptosis, and renal fibrosis by GOLPH3 inhibition with siRNA in CaOx-stimulated HK-2 cells. The PI3K\AKT\mTOR signaling pathway was inhibited by GOLPH3 knockdown, which may be associated with reduced inflammatory response and apoptosis, as well as restoration of Golgi morphology and function. In conclusion, GOLPH3 plays a critical role in CaOx-induced kidney injury by promoting Golgi stress and increasing inflammatory responses, apoptosis, and renal fibrosis, suggesting that GOLPH3 is a potential therapeutic target for kidney stones. |
| format | Article |
| id | doaj-art-1a5f9d00a72e40368126fa0b97bdfc1b |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-1a5f9d00a72e40368126fa0b97bdfc1b2025-08-20T01:57:44ZengNature PortfolioScientific Reports2045-23222025-03-0115111310.1038/s41598-025-91638-0GOLPH3 promotes calcium oxalate-induced renal injury and fibrosis through Golgi stress-mediated apoptosis and inflammatory responsesBao-feng Song0Bo-jun Li1Yushi Sun2Ming Li3Ting Rao4Yuan Ruan5Fan Cheng6Department of Urology, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityAbstract A common urological disorder, calcium oxalate (CaOx) stones are the most common form of kidney stones. Deposition of CaOx crystals leads to tubular damage, interstitial fibrosis, and chronic kidney disease. Understanding the intrinsic mechanisms of kidney stone formation is essential for the prevention of kidney stones and the development of new therapeutic agents. The Golgi apparatus is a key organelle in the secretory pathway of eukaryotic cells, which plays an important role in the sorting, modification, and transport of proteins within the cell, and has been reported to be involved in several diseases, including prostate tumors, gastrointestinal tumors, sepsis, and so on. GOLPH3 is also known as GPP34, GMx33, or MIDAS. It is a glycoprotein that regulates traffic between the trans-Golgi network and the cell membrane. However, its role in renal injury caused by CaOx crystal deposition is still unclear. Results from immunohistochemistry, qRT-PCR, western blot, and public database single nucleotide RNA-seq showed that GOLPH3 was significantly upregulated in kidney stone patients and animal kidneys. Significant inhibition of Golgi stress, apoptosis, and renal fibrosis by GOLPH3 inhibition with siRNA in CaOx-stimulated HK-2 cells. The PI3K\AKT\mTOR signaling pathway was inhibited by GOLPH3 knockdown, which may be associated with reduced inflammatory response and apoptosis, as well as restoration of Golgi morphology and function. In conclusion, GOLPH3 plays a critical role in CaOx-induced kidney injury by promoting Golgi stress and increasing inflammatory responses, apoptosis, and renal fibrosis, suggesting that GOLPH3 is a potential therapeutic target for kidney stones.https://doi.org/10.1038/s41598-025-91638-0Kidney stonesCaOxGOLPH3Golgi |
| spellingShingle | Bao-feng Song Bo-jun Li Yushi Sun Ming Li Ting Rao Yuan Ruan Fan Cheng GOLPH3 promotes calcium oxalate-induced renal injury and fibrosis through Golgi stress-mediated apoptosis and inflammatory responses Scientific Reports Kidney stones CaOx GOLPH3 Golgi |
| title | GOLPH3 promotes calcium oxalate-induced renal injury and fibrosis through Golgi stress-mediated apoptosis and inflammatory responses |
| title_full | GOLPH3 promotes calcium oxalate-induced renal injury and fibrosis through Golgi stress-mediated apoptosis and inflammatory responses |
| title_fullStr | GOLPH3 promotes calcium oxalate-induced renal injury and fibrosis through Golgi stress-mediated apoptosis and inflammatory responses |
| title_full_unstemmed | GOLPH3 promotes calcium oxalate-induced renal injury and fibrosis through Golgi stress-mediated apoptosis and inflammatory responses |
| title_short | GOLPH3 promotes calcium oxalate-induced renal injury and fibrosis through Golgi stress-mediated apoptosis and inflammatory responses |
| title_sort | golph3 promotes calcium oxalate induced renal injury and fibrosis through golgi stress mediated apoptosis and inflammatory responses |
| topic | Kidney stones CaOx GOLPH3 Golgi |
| url | https://doi.org/10.1038/s41598-025-91638-0 |
| work_keys_str_mv | AT baofengsong golph3promotescalciumoxalateinducedrenalinjuryandfibrosisthroughgolgistressmediatedapoptosisandinflammatoryresponses AT bojunli golph3promotescalciumoxalateinducedrenalinjuryandfibrosisthroughgolgistressmediatedapoptosisandinflammatoryresponses AT yushisun golph3promotescalciumoxalateinducedrenalinjuryandfibrosisthroughgolgistressmediatedapoptosisandinflammatoryresponses AT mingli golph3promotescalciumoxalateinducedrenalinjuryandfibrosisthroughgolgistressmediatedapoptosisandinflammatoryresponses AT tingrao golph3promotescalciumoxalateinducedrenalinjuryandfibrosisthroughgolgistressmediatedapoptosisandinflammatoryresponses AT yuanruan golph3promotescalciumoxalateinducedrenalinjuryandfibrosisthroughgolgistressmediatedapoptosisandinflammatoryresponses AT fancheng golph3promotescalciumoxalateinducedrenalinjuryandfibrosisthroughgolgistressmediatedapoptosisandinflammatoryresponses |