Transforming growth factor beta increases the expression of HIV-1 gene in transfected human mesangial cells.
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)
Shukla
R R
RR
Department of Molecular Biology, George Washington University Medical Center, Washington, D.C.
Kumar
A
A
Kimmel
P L
PL
D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D005920:Glomerular Mesangium / Q000166:cytology / Q000502:physiology*; D006133:Growth Substances / Q000494:pharmacology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D010455:Peptides / Q000494:pharmacology; D012091:Repetitive Sequences, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D006133:Growth Substances; D010455:Peptides; D014157:Transcription Factors; D016212:Transforming Growth Factor beta