Transforming growth factor beta increases the expression of HIV-1 gene in transfected human mesangial cells

Abstract

Human immunodeficiency virus type 1 (HIV) infection is often complicated by focal glomerulosclerosis (FGS) and other renal lesions collectively termed HIV associated nephropathy (HIVAN). FGS is characterized by glomerular mesangial expansion and increased synthesis of matrix components. The molecular pathogenic mechanisms associated with the development of HIV associated nephropathy are unknown. Experimental animal models suggest a role for cytokines and growth factors, particularly transforming growth factor beta (TGF-beta), in the pathogenesis of glomerulosclerosis. Patients with AIDS have elevated plasma and tissue levels of TGF-beta. We carried out experiments to determine whether primary human mesangial cells (HMC) in culture can be transfected with HIV-1 genes. HMC were transfected with a chloramphenicol acetyl transferase (CAT) reporter construct containing HIV-1 acetyl transferase (CAT) reporter construct containing HIV-1 LTR sequences. Our results show successful transfection of HMC with HIV-1 LTR gene. HMC transfected with LTR gene are responsive to the HIV-1 regulatory gene product Tat. To study whether TGF-beta can modulate the expression of HIV-1 LTR gene in HMC, HMC transfected with an HIV-1 LTR CAT plasmid were treated with TGF-beta and other growth factors two hours before harvest. TGF-beta specifically increased the expression of the HIV-1 gene in HMC in a dose dependent manner. We further studied whether up-regulation of HIV-1 LTR expression in HMC was mediated by the effect of TGF-beta on the interaction of transcription factors to their binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

p300 Modulates HIV-1 gp120-Induced Apoptosis in Human Proximal Tubular Cells: Associated with Alteration of TGF-β and Smad Signaling

“…It has been known that TGF-β plays a very important regulatory role in cell growth [38,39]. Moreover, its role in the pathogenesis of HIVAN at various stages and an intermediary role in the cytopathogenesity of HIV-1 have been suggested previously [9, 10]. Increased expression of TGF-β is found in HIVAN [9, 10].…”

“…Moreover, its role in the pathogenesis of HIVAN at various stages and an intermediary role in the cytopathogenesity of HIV-1 have been suggested previously [9, 10]. Increased expression of TGF-β is found in HIVAN [9, 10]. Patients with AIDS also show elevated levels of TGF-β in their plasma and tissue [10].…”

“…Increased expression of TGF-β is found in HIVAN [9, 10]. Patients with AIDS also show elevated levels of TGF-β in their plasma and tissue [10]. Over-production of TGF-β in transgenic mice for HIV-1 gene has been incriminated for mesangial cell proliferation and matrix accumulation [40].…”

“…TGF-β has been suggested to play a role in the pathogenesis of HIVAN at various stages [9,10,11]. Smad family members are essential intracellular signaling components of the TGF-β superfamily involved in a range of biological activities [12,13,14,15].…”

Inhibition of Notch pathway attenuates the progression of human immunodeficiency virus-associated nephropathy

“…Many signaling pathways including Wnt, TGF-␤, Stat3, and mTOR pathway have been shown to be involved in HIVAN progression (20,24,43,45,48). Interestingly, many of these pathways have also been shown to interact with the Notch pathway (9,28,34).…”