Proliferation of cyst-lining epithelial cells is an integral part of autosomal dominant polycystic kidney disease (ADPKD) cyst growth. Cytokines and growth factors within cyst fluids are positioned to induce cyst growth. Vascular endothelial growth factor (VEGF) is a pleiotropic growth factor present in ADPKD liver cyst fluids (human 1,128 ± 78, mouse 2,787 ± 136 pg/ml) and, to a lesser extent, in ADPKD renal cyst fluids (human 294 ± 41, mouse 191 ± 90 pg/ml). Western blotting showed that receptors for VEGF (VEGFR1 and VEGFR2) were present in both normal mouse bile ducts and pkd2(WS25/−) liver cyst epithelial cells. Treatment of pkd2(WS25/−) liver cyst epithelial cells with VEGF (50–50,000 pg/ml) or liver cyst fluid induced a proliferative response. The effect on proliferation of liver cyst fluid was inhibited by SU-5416, a potent VEGF receptor inhibitor. Treatment of pkd2(WS25/−) mice between 4 and 8 mo of age with SU-5416 markedly reduced the cyst volume density of the liver (vehicle 9.9 ± 4.3%, SU-5416 1.8 ± 0.7% of liver). SU-5416 treatment between 4 and 12 mo of age markedly protected against increases in liver weight [pkd2(+/+) 4.8 ± 0.2%, pkd2(WS25/−)-vehicle 10.8 ± 1.9%, pkd2(WS25/−)-SU-5416 4.8 ± 0.4% body wt]. The capacity of VEGF signaling to induce in vitro proliferation of pkd2(WS25/−) liver cyst epithelial cells and inhibition of in vivo VEGF signaling to retard liver cyst growth in pkd2(WS25/−) mice indicates that the VEGF signaling pathway is a potentially important therapeutic target in the treatment of ADPKD liver cyst disease.
The autoimmune disease, rheumatoid arthritis (RA), leads to joint pain and inflammation. Pharmaceutical drugs, including methotrexate, as well as antibodies directed against inflammatory cytokines (“biologics”) are frequently used to combat this disease. Diet and dietary supplement use is a common symptom self‐management approach among RA patients, but the identity and frequency of specific types of dietary approaches used is currently unknown. To better understand this, we developed an anonymous, online or in‐clinic survey reporting use of individual pharmaceuticals, dietary supplements (vitamins, minerals, or natural products), and dietary approaches by RA patients for their symptom management. Responses were collected primarily using community‐(vs. clinic‐) based outreach in Tucson, Arizona. Cross‐sectional analysis of data reported here is for use of specific medications, supplements, or foods for symptom management from individuals with self‐reported RA (n= 206). Most participants were middle aged (57.4 ± 12.9 years), non‐Hispanic (82%, n= 168), Caucasian (86%, n= 178) and female (91%, n= 188). Almost all individuals reported living in the U.S. (96%, n= 197), with the majority residing in Arizona (67.0%, n= 138). Current methotrexate or biologic use was reported by 42% (n= 86) and 24% (n= 50) of respondents, respectively. Vitamin and/or mineral use for RA management was reported by 85% (n= 176). The following had the highest reported current use: vitamin D (54%, n= 112), folate (39%; n=80), calcium (35%, n= 73), multivitamins (34%, n= 69), and vitamin B12 (21%, n= 44). Non‐vitamin/mineral, natural product supplement use for RA management was reported by 63% of respondents (n= 129). Of these, turmeric (29%, n= 60), fish oil (25%, n= 52), ginger (13%, n= 26), flaxseed (12%, n= 24), and glucosamine/chondroitin (9%, n= 19) were the top currently used. Dietary approaches for RA management were reported by 28% of participants (n= 57); green tea (12%, n= 25), turmeric tea (11%, n= 23), gluten‐free diet (9%, n= 19), coconut oil (6%, n= 12), and paleo diet (4%, n= 9) were the most common dietary approaches in current use. In summary, alternative strategies for RA self‐management were prevalent, with turmeric‐derived products being the most frequently used natural product dietary supplement, as well as a common component of diet‐based approaches. Additional information regarding the safety and efficacy of turmeric in a RA population is warranted.
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