Role of SIRT1 in HIV-associated kidney disease.

Role of SIRT1 in HIV-associated kidney disease. Am J Physiol Renal Physiol. 2020 Jul 13;: Authors: Wang X, Liu R, Zhang W, Hyink DP, Das GC, Das B, Li Z, Wang A, Yuan W, Klotman PE, Lee K, He JC Abstract HIV infection of kidney cells can lead to HIV-associated nephropathy (HIVAN) and aggravate the progression of other chronic kidney diseases. Thus, a better understanding of the mechanisms of HIV-induced kidney cell injury is needed for effective therapy against HIV-induced kidney disease progression. We previously showed that the acetylation and activation of key inflammatory regulators, NF-κB p65 and STAT3 were increased in HIVAN kidneys. Here, we demonstrate the key role of SIRT1 deacetylase in the regulation of NF-κB and STAT3 activity in HIVAN. We found that SIRT1 expression was reduced in the glomeruli of human and mouse HIVAN kidneys and that HIV-1 gene expression was associated with reduced SIRT1 expression and increased acetylation of NF-κB p65 and STAT3in cultured podocytes. Interestingly, SIRT1 overexpression, in turn, reduced the expression of Nef in podocytes stably expressing the HIV1 proviral genes, which was associated with the inactivation of NF-κB p65 and reduction in the HIV1 LTR promoter activity. In vivo, the administration of small molecule SIRT1 agonist BF175 or inducible overexpression of SIRT1 specifically in podocytes markedly attenuated albuminuria, kidney lesions, and expression of inflammatory markers ...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research