Article ; Online: TRPM7 in CHBP-induced renoprotection upon ischemia reperfusion-related injury.
2018 Volume 8, Issue 1, Page(s) 5510
Abstract: ... involved not only in IR-related injury, but also CHBP-induced renoprotection, which are ... subjected to 30-min ischemia and 12-h to 7-day reperfusion. TRPM7-like current in TCMK-1 cells, TRPM7 mRNA ... abundantly expressed in the kidney, and up-regulated by ischemia reperfusion (IR) injury. Our previous ...
| Abstract | Transient receptor potential melastatin 7 (TRPM7) is a membrane ion channel and kinase. TRPM7 was abundantly expressed in the kidney, and up-regulated by ischemia reperfusion (IR) injury. Our previous studies showed that cyclic helix B peptide (CHBP) improved renal IR-related injury, but its underlying mechanism is not well defined. IR-related injury was established in renal tubular epithelial cells (TCMK-1 and HK-2) via 12 to 24-h hypoxia (H) followed by 2-24 h reoxygenation (R), and in mouse kidneys subjected to 30-min ischemia and 12-h to 7-day reperfusion. TRPM7-like current in TCMK-1 cells, TRPM7 mRNA and protein in the in vitro and in vivo models were increased, but reversed by CHBP. TRPM7 was also positively associated with LDH, HMGB1, caspase-3, Bax/Bcl-2, inflammation, apoptosis, tubulointerstitial damage and renal function respectively. Furthermore, silencing TRPM7 improved injury parameters, renal histology and function in the both models. Specific TRPM7 agonist, bradykinin, exaggerated HR induced injury in TCMK-1 cells, and partially blocked the renoprotection of CHBP as well. In conclusion, TRPM7 is involved not only in IR-related injury, but also CHBP-induced renoprotection, which are through its ion channel and subsequent affects inflammation and apoptosis. Therefore, TRPM7 could be a potential biomarker for IR-induced acute kidney injury. |
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| MeSH term(s) | Animals ; Apoptosis/drug effects ; Cell Line ; Gene Expression/drug effects ; Gene Silencing ; Humans ; Kidney/drug effects ; Kidney/injuries ; Kidney/metabolism ; Kidney/pathology ; Kidney Tubules/drug effects ; Kidney Tubules/pathology ; Mice ; Peptides, Cyclic/pharmacology ; Protein-Serine-Threonine Kinases/deficiency ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; RNA, Small Interfering/genetics ; Reperfusion Injury/genetics ; Reperfusion Injury/metabolism ; Reperfusion Injury/pathology ; TRPM Cation Channels/deficiency ; TRPM Cation Channels/genetics ; TRPM Cation Channels/metabolism |
| Chemical Substances | Peptides, Cyclic ; RNA, Small Interfering ; TRPM Cation Channels ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; TRPM7 protein, human (EC 2.7.11.1) |
| Language | English |
| Publishing date | 2018-04-03 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2615211-3 |
| ISSN | 2045-2322 ; 2045-2322 |
| ISSN (online) | 2045-2322 |
| ISSN | 2045-2322 |
| DOI | 10.1038/s41598-018-22852-2 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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