Glomerular MYH9 expression is reduced by HIV-1.
BACKGROUND
The continuing disease burden of HIV-associated nephropathy (HIVAN) warrants better elucidation of its pathogenic mechanisms. Given that loss of MYH9 function causes a Mendelian renal disease, we hypothesized that renal expression of MYH9 is down-regulated by HIV-1 in HIVAN pathogenesis.


RESULTS
Using immunofluorescence, we determined that glomerular expression of MYH9 was reduced in the kidneys of HIV-1 transgenic mice. We further determined that Myh9 expression was reduced in HIV-1 transgenic podocytes, statistically significantly at the protein level, and that MYH9 expression was significantly reduced at protein and message level in human podocytes transduced with HIV-1. In analyzing expression in human tissue, we confirmed that MYH9 is abundantly expressed in glomeruli, and podocytes specifically. Finally, we found that MYH9 expression was significantly reduced in human glomeruli in the setting of HIVAN.


CONCLUSIONS
We conclude that the podocyte host response to HIV-1 includes down-regulation of MYH9 expression, and hypothesize that this down-regulation might play a role in the pathogenesis of HIVAN.
Mount Sinai School of Medicine, Department of Medicine, New York, New York, USA. thomas.hays@mssm.edu
Thomas
T
Hays
Vivette D
VD
D'Agati
Jonathan A
JA
Garellek
Tjani
T
Warren
Marc E
ME
Trubin
Deborah P
DP
Hyink
John Cijiang
JC
He
Paul E
PE
Klotman
D016263:AIDS-Associated Nephropathy / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D015658:HIV Infections / Q000378:metabolism / Q000503:physiopathology; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D020409:Molecular Motor Proteins / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism*; D050199:Podocytes / Q000378:metabolism / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction
C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; C525088:Myh9 protein, mouse; D024507:Nonmuscle Myosin Type IIA; D018995:Myosin Heavy Chains