Mice with cav-1 gene disruption have benign stromal lesions and compromised epithelial differentiation.
Caveolin-1 (cav-1) is a major structural protein of caveolae, small invaginations of the plasma membrane that integrate and regulate signaling pathways involved in cell growth and differentiation. We previously generated a genetically engineered mice that are homozygous for a null mutation in exon 2 of cav-1 and documented increased incidence of urolithiasis in young male cav-1(-/-) mice. We attributed this, in part, to improper localization of plasma membrane calcium/calmodulin-dependent calcium ATPase in the distal convoluted tubules of the kidney. To document pathologies related to cav-1 function, we maintained cav-1(-/-) and control cav-1(+/+) mice for an extended time period. We report here that cav-1(-/-) mice demonstrate organ-specific growth-related disorders in stromal cells that normally have high levels of cav-1 expression. In many of these organs, epithelial cell growth/differentiation abnormalities were also observed, yet in most of these sites the epithelial cells normally express low to non-detectable levels of cav-1. We propose that loss of cav-1 function in stromal cells of various organs directly leads to a disorganized stromal compartment that, in turn, indirectly promotes abnormal growth and differentiation of adjacent epithelium.
Yang
Guang
G
Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA.
Timme
Terry L
TL
Naruishi
Koji
K
Fujita
Tetsuo
T
Fattah
El Moataz Abdel
el MA
Cao
Guangwen
G
Rajagopalan
Kartik
K
Rajocopolan
Kartik
K
Troung
Luan D
LD
Thompson
Timothy C
TC
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D051242:Caveolin 1 / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D020868:Gene Silencing; D005835:Genitalia / Q000378:metabolism / Q000473:pathology; D007633:Keratins / Q000378:metabolism; D008136:Longevity; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers; D051242:Caveolin 1; D007633:Keratins