| First Author | Abousaad S | Year | 2022 |
| Journal | Physiol Rep | Volume | 10 |
| Issue | 18 | Pages | e15468 |
| PubMed ID | 36117389 | Mgi Jnum | J:329305 |
| Mgi Id | MGI:7343173 | Doi | 10.14814/phy2.15468 |
| Citation | Abousaad S, et al. (2022) Meprin beta expression modulates the interleukin-6 mediated JAK2-STAT3 signaling pathway in ischemia/reperfusion-induced kidney injury. Physiol Rep 10(18):e15468 |
| abstractText | Meprin metalloproteinases have been implicated in the pathophysiology of ischemia/reperfusion (IR)-induced kidney injury. Previous in vitro data showed that meprin beta proteolytically processes interleukin-6 (IL-6) resulting in its inactivation. Recently, meprin-beta was also shown to cleave the IL-6 receptor. The goal of this study was to determine how meprin beta expression impacts IL-6 and downstream modulators of the JAK2-STAT3-mediated signaling pathway in IR-induced kidney injury. IR was induced in 12-week-old male wild-type (WT) and meprin beta knockout (betaKO) mice and kidneys obtained at 24 h post-IR. Real-time PCR, western blot, and immunostaining/microscopy approaches were used to quantify mRNA and protein levels respectively, and immunofluorescence counterstaining with proximal tubule (PT) markers to determine protein localization. The mRNA levels for IL-6, CASP3 and BCL-2 increased significantly in both genotypes. Interestingly, western blot data showed increases in protein levels for IL-6, CASP3, and BCL-2 in the betaKO but not in WT kidneys. However, immunohistochemical data showed increases in IL-6, CASP3, and BCL-2 proteins in select kidney tubules in both genotypes, shown to be PTs by immunofluorescence counterstaining. IR-induced increases in p-STAT-3 and p-JAK-2 in betaKO at a global level but immunoflourescence counterstaining demonstrated p-JAK2 and p-STAT3 increases in select PT for both genotypes. BCL-2 increased only in the renal corpuscle of WT kidneys, suggesting a role for meprins expressed in leukocytes. Immunohistochemical analysis confirmed higher levels of leukocyte infiltration in WT kidneys when compared to betaKO kidneys. The present data demonstrate that meprin beta modulates IR-induced kidney injury in part via IL-6/JAK2/STAT3-mediated signaling. |
