| First Author | Yang X | Year | 2021 |
| Journal | Sci Rep | Volume | 11 |
| Issue | 1 | Pages | 11146 |
| PubMed ID | 34045489 | Mgi Jnum | J:306280 |
| Mgi Id | MGI:6713183 | Doi | 10.1038/s41598-021-89983-x |
| Citation | Yang X, et al. (2021) DHHC21 deficiency attenuates renal dysfunction during septic injury. Sci Rep 11(1):11146 |
| abstractText | Renal dysfunction is one of the most common complications of septic injury. One critical contributor to septic injury-induced renal dysfunction is renal vascular dysfunction. Protein palmitoylation serves as a novel regulator of vascular function. Here, we examined whether palmitoyl acyltransferase (PAT)-DHHC21 contributes to septic injury-induced renal dysfunction through regulating renal hemodynamics. Multispectral optoacoustic imaging showed that cecal ligation and puncture (CLP)-induced septic injury caused impaired renal excretion, which was improved in DHHC21 functional deficient (Zdhhc21(dep/dep)) mice. DHHC21 deficiency attenuated CLP-induced renal pathology, characterized by tissue structural damage and circulating injury markers. Importantly, DHHC21 loss-of-function led to better-preserved renal perfusion and oxygen saturation after CLP. The CLP-caused reduction in renal blood flow was also ameliorated in Zdhhc21(dep/dep) mice. Next, CLP promoted the palmitoylation of vascular alpha1-adrenergic receptor (alpha1AR) and the activation of its downstream effector ERK, which were blunted in Zdhhc21(dep/dep) mice. Vasoreactivity analysis revealed that renal arteries from Zdhhc21(dep/dep) mice displayed reduced constriction response to alpha1AR agonist phenylephrine compared to those from wild-type mice. Consistently, inhibiting PATs with 2-bromopalmitate caused a blunted vasoconstriction response to phenylephrine in small arteries isolated from human kidneys. Therefore, DHHC21 contributes to impaired renal perfusion and function during septic injury via promoting alpha1AR palmitoylation-associated vasoconstriction. |
