Nicotine: The Link Between
Cigarette Smoking and Kidney Disease Progression?
(BETHESDA, MD) -- Cigarette smoke (CS) is the
most preventable cause of death and chronic disease in the United States. In
addition to being a risk factor for atherosclerosis and cancer, recent
epidemiologic studies suggest that cigarette smoke promotes the progression
of kidney disease.
The mechanisms by which cigarette smoke may accelerate
some types of chronic kidney disease are currently unknown. A new study,
being published by the American Physiological Society (http://www.the-aps.org/),
demonstrates for the first time that human mesangial cells (MC) – cells in
the blood vessels of the kidneys – are endowed with nicotinic receptors (nAChRs)
α4, α5, α7, β2, β3, β4 and β5 (cells that interact with the nicotine in
tobacco) and may play an active role in the development of certain kidney
diseases.
The Study
The study, “Nicotine: The Link Between Cigarette
Smoking and the Progression of Renal Injury?,” was conducted by Edgar A.
Jaimes, MD, Run-Xia Tian, MD, and Leopoldo Raij, MD, all of the Miller
School of Medicine, University of Miami, Miami, FL. It appears in the
Articles in Press Section of the American Journal of Physiology –
Heart and Circulatory Physiology (http://ajpheart.physiology.org/),
one of 11-peer reviewed journals published by the APS.
Overview of Methodology
Human mesangial cells were grown in CSC-Complete media,
supplemented with 10 percent fetal calf serum. Cells were passed by
trypsinization when confluent and used between the third and ninth passages.
3H-thymidine was used as an index of cell proliferation and cells
were fasted for 72 hours in Maintenance Media and stimulated for 24 hours
with nicotine (10-10 M to 10-7 M) or platelet derived
growth factor.
Western blots were performed after the cells fasted and
had been stimulated for 24 hours with nicotine (10-7). Cell
homogenates were washed and thereafter centrifuged for 30 minutes. Blots
were incubated overnight with one of nine antibodies, which included mouse
anti-α2-nAChR mAb’s, anti-α3-nAChR mAb’s, or anti-α4-nAChR mAb’s.
Fibronectin mRNA expression was determined by real time PCR and protein
expression was measured by western blot. Flow cytometry measurement was
generated for reactive oxygen species.
Data were expressed as mean ± SEM. For statistical
comparisons involving two groups, an unpaired Student t test was
used. For comparisons involving more than two groups, ANOVA was used.
Significance was considered when P<0.05.
Highlights of Results
Highlights of the results include the following:
Human mesangial cells express nAChRs: The
researchers were able to detect strong expression of several nAChRs subunits
in the cultured human mesangial cells. They detected the presence of the
nAChRs subunits α4, α5, α7, β2, β3, and β4 in these cells. They were not,
however, able to detect significant expression of the α2 or α3 nAChR
subunits.
Nicotine increases mesangial cell proliferation via
nAChRs activation: Nicotine stimulation of the cells resulted in a dose
dependent increase in mesangial cell proliferation. One concentration found
in the plasma of active smokers found that nicotine-induced MC proliferation
was 1,328 for controls vs. 2,761 for nicotine.
Nicotine increases fibronectin production: To
determine whether transcriptional mechanisms were involved, the researchers
measured the gene expression of fibronectin using real time exposure to
nicotine. They found that nicotine induced a five-fold increase in
fibronectin mRNA expression.
Summary and Conclusions
These studies are believed to be the first of their
kind to:
(1)
identify the presence of functionally active nAChRs in human
mesangial cells; and
(2)
demonstrate that nicotine, at concentrations similar to those found
in the plasma of smokers, promotes mesangial cell proliferation and spurs on
critical molecules that are involved in the extracellular matrix production.
Recent epidemiologic studies demonstrate that cigarette
smoking increases the risk for progressive chronic kidney disease, but the
role of smoking in primary renal diseases is less known. The results of
this research, coupled with earlier findings, reveal previously unrecognized
mechanisms showing nicotine – a component of cigarette smoke – as an agent
that may accelerate and promote the progression of chronic kidney disease.
***
JOURNAL PUBLICATION INFORMATION
American Journal of Physiology – Heart and
Circulatory Physiology, (Articles in Press)
http://ajpheart.physiology.org/.
NOTE TO EDITORS
To schedule an interview with a member of the research
team, please contact Donna Krupa at 301.634.7209 (direct dial), 703.967.2751
(cell) or
dkrupa@The-APS.org.
Physiology is the study of how molecules,
cells, tissues and organs function to create health or disease. The American
Physiological Society (APS) has been an integral part of this scientific
discovery process since it was established in 1887.
