| First Author | Poveda J | Year | 2016 |
| Journal | Biochim Biophys Acta | Volume | 1862 |
| Issue | 4 | Pages | 635-646 |
| PubMed ID | 26776679 | Mgi Jnum | J:255633 |
| Mgi Id | MGI:6105102 | Doi | 10.1016/j.bbadis.2016.01.006 |
| Citation | Poveda J, et al. (2016) NFkappaBiz protein downregulation in acute kidney injury: Modulation of inflammation and survival in tubular cells. Biochim Biophys Acta 1862(4):635-646 |
| abstractText | Acute kidney injury is characterized by decreased renal function, tubular cell death and interstitial inflammation. The transcription factor NF-kappaB is a key regulator of genes involved in cell survival and the inflammatory response. In order to better understand the regulation and role of NF-kappaB in acute kidney injury we explored the expression of NF-kappaB-related genes in experimental acute kidney injury induced by a folic acid overdose. NFkappaBiz, a member of the IkappaB family of NF-kappaB regulators encoding NFkappaBiz, was among the top up-regulated NF-kappaB-related genes at the mRNA level in experimental acute kidney injury. However, the NFkappaBiz protein was constitutively expressed by normal tubular cells but was down-regulated in experimental acute kidney injury. Kidney NFkappaBiz mRNA upregulation and protein downregulation was also observed in acute kidney injury induced by cisplatin or unilateral kidney injury resulting from ureteral obstruction. Thus, we studied the consequences of NFkappaBiz protein downregulation by specific siRNA in cultured tubular epithelial cells. NFkappaBiz mRNA and protein were up-regulated by inflammatory cytokines (IL-1beta or TWEAK/TNFalpha/IFNgamma) and by LPS in cultured tubular cells. However, TWEAK only induced a very mild and short lived NFkappaBiz upregulation. NFkappaBiz targeting increased chemokine production and dampened Klotho downregulation induced by TWEAK, without modulating cell proliferation. NFkappaBiz targeting also rendered cells more resistant to apoptosis induced by serum deprivation or inflammatory cytokines. In conclusion, NFkappaBiz differentially regulates NF-kappaB-mediated responses of tubular cells to inflammatory cytokines in a gene-specific manner, and may be of potential therapeutic interest to limit inflammation in kidney disease. |
