Discovery and verification of mmu_Circ_26986/hsa_Circ_0072463 as a potential biomarker and intervention target for sepsis-associated acute kidney injury
Abstract Approximately 60% of septic patients developed acute kidney injury (AKI). The mortality rate of septic AKI (SA-AKI) is two to three times higher than that of septic without AKI (SA-non-AKI). The actual functions and mechanisms of CircRNAs in the pathophysiology of SA-AKI remain incompletely understood. Herein, we observed that the mmu_Circ_26986 could be induced by lipopolysaccharide (LPS) and cecum ligation and puncture (CLP) in BUMPT cell line and C57BL/6 mouse kidney, respectively. Functionally, mmu_Circ_26986 suppressed BUMPT cell apoptosis induced by LPS. Mechanistically, mmu_Circ_26986 sponged miRNA-29b-1-5p to upregulate the expression of PAK7. Overexpression of mmu_Circ_26986 ameliorated the progression of CLP-stimulated AKI through miRNA-29b-1-5p/PAK7 axis. In addition, we found that hsa_Circ_0072463, homologous to mmu_Circ_26986, suppressed LPS-induced HK-2 cells apoptosis via regulation of miRNA-29b-1-5p/PAK7 axis. Furthermore, sepsis patients with AKI had a higher level of hsa_Circ_0072463 compared to those without AKI. The sensitivity, specificity and AUC of hsa_Circ_0072463 were 78.8%, 87.9% and 0.866, respectively. Spearman's test indicated a noticeable positive correlation between plasma hsa_Circ_0072463 and serum creatinine in sepsis patients (r = 0.725). In summary, this study reveals that the mmu_Circ_26986/hsa_Circ_0072463 miRNA-29b-1-5p/PAK7 axis mediates septic AKI, and hsa_Circ_0072463 is a potential diagnostic marker for septic AKI..
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:81 |
|---|---|
| Enthalten in: |
Cellular and molecular life sciences - 81(2024), 1 vom: 28. März |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Peng, Xujun [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| BKL: | |
|---|---|
| Themen: |
AKI |
| Anmerkungen: |
© The Author(s) 2024 |
|---|
| doi: |
10.1007/s00018-023-05079-x |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
SPR05531421X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | SPR05531421X | ||
| 003 | DE-627 | ||
| 005 | 20240328072108.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240328s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s00018-023-05079-x |2 doi | |
| 035 | |a (DE-627)SPR05531421X | ||
| 035 | |a (SPR)s00018-023-05079-x-e | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 570 |a 610 |q VZ |
| 084 | |a 42.15 |2 bkl | ||
| 100 | 1 | |a Peng, Xujun |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Discovery and verification of mmu_Circ_26986/hsa_Circ_0072463 as a potential biomarker and intervention target for sepsis-associated acute kidney injury |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a © The Author(s) 2024 | ||
| 520 | |a Abstract Approximately 60% of septic patients developed acute kidney injury (AKI). The mortality rate of septic AKI (SA-AKI) is two to three times higher than that of septic without AKI (SA-non-AKI). The actual functions and mechanisms of CircRNAs in the pathophysiology of SA-AKI remain incompletely understood. Herein, we observed that the mmu_Circ_26986 could be induced by lipopolysaccharide (LPS) and cecum ligation and puncture (CLP) in BUMPT cell line and C57BL/6 mouse kidney, respectively. Functionally, mmu_Circ_26986 suppressed BUMPT cell apoptosis induced by LPS. Mechanistically, mmu_Circ_26986 sponged miRNA-29b-1-5p to upregulate the expression of PAK7. Overexpression of mmu_Circ_26986 ameliorated the progression of CLP-stimulated AKI through miRNA-29b-1-5p/PAK7 axis. In addition, we found that hsa_Circ_0072463, homologous to mmu_Circ_26986, suppressed LPS-induced HK-2 cells apoptosis via regulation of miRNA-29b-1-5p/PAK7 axis. Furthermore, sepsis patients with AKI had a higher level of hsa_Circ_0072463 compared to those without AKI. The sensitivity, specificity and AUC of hsa_Circ_0072463 were 78.8%, 87.9% and 0.866, respectively. Spearman's test indicated a noticeable positive correlation between plasma hsa_Circ_0072463 and serum creatinine in sepsis patients (r = 0.725). In summary, this study reveals that the mmu_Circ_26986/hsa_Circ_0072463 miRNA-29b-1-5p/PAK7 axis mediates septic AKI, and hsa_Circ_0072463 is a potential diagnostic marker for septic AKI. | ||
| 650 | 4 | |a mmu_Circ_26986 |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a hsa_Circ_0072463 |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Biomaker |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a AKI |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a SA-AKI |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Apoptosis |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a LPS |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a CLP |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a miRNA-29b-1-5p |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a PAK7 |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Li, Huiling |4 aut | |
| 700 | 1 | |a Zhang, Wenbo |4 aut | |
| 700 | 1 | |a Zhang, Dongshan |0 (orcid)0000-0002-7387-4804 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cellular and molecular life sciences |d Springer International Publishing, 1997 |g 81(2024), 1 vom: 28. März |w (DE-627)SPR00008039X |w (DE-600)1458497-9 |x 1420-9071 |7 nnns |
| 773 | 1 | 8 | |g volume:81 |g year:2024 |g number:1 |g day:28 |g month:03 |
| 856 | 4 | 0 | |u https://dx.doi.org/10.1007/s00018-023-05079-x |z kostenfrei |3 Volltext |
| 912 | |a GBV_SPRINGER | ||
| 912 | |a SSG-OLC-PHA | ||
| 936 | b | k | |a 42.15 |q VZ |
| 951 | |a AR | ||
| 952 | |d 81 |j 2024 |e 1 |b 28 |c 03 | ||