Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autosomal recessive polycystic kidney disease (ARPKD) is a monogenic disease characterized by development of hepatorenal cysts, pericystic fibrosis, and inflammation. Previous studies show that mast cell (MC) mediators such as histamine induce proliferation of cholangiocytes. We observed robust MC accumulation around liver cysts, but not kidney cysts, in polycystic kidney (PCK) rats (an animal model of ARPKD). Therefore, we hypothesized that MCs contribute to hepatic cyst growth in ARPKD. To test this hypothesis, we treated PCK rats with 1 of 2 different MC stabilizers, cromolyn sodium (CS) or ketotifen, or saline. The CS treatment decreased MC degranulation in the liver and reduced serum tryptase (an MC granule component). Interestingly, we observed an increase in liver to body weight ratio after CS treatment paralleled by a significant increase in individual cyst size. Hepatic fibrosis was not affected by CS treatment. The CS treatment increased hepatic cyst wall epithelial cell (CWEC) proliferation and decreased cell death. Ketotifen treatment also increased hepatic cyst size. In vitro, CS treatment did not affect proliferation of isolated hepatic CWECs from PCK rats. In contrast, CS decreased kidney to body weight ratio paralleled by a significant decrease in individual cyst size. The percentage of kidney to body weight ratio was strongly correlated with serum renin (an MC granule component). Ketotifen did not affect kidney cyst growth. Collectively, these data suggest that CS affects hepatic and renal cyst growth differently in PCK rats. Moreover, CS may be beneficial to renal cystic disease but may exacerbate hepatic cyst growth in ARPKD.
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PMID:Inhibition of Mast Cell Degranulation With Cromolyn Sodium Exhibits Organ-Specific Effects in Polycystic Kidney (PCK) Rats. 2986 68

Glycogen storage disease type I (GSDI) is a rare genetic pathology characterized by glucose-6 phosphatase (G6Pase) deficiency, translating in hypoglycemia during short fasts. Besides metabolic perturbations, GSDI patients develop long-term complications, especially chronic kidney disease (CKD). In GSDI patients, CKD is characterized by an accumulation of glycogen and lipids in kidneys, leading to a gradual decline in renal function. At a molecular level, the activation of the renin-angiotensin system is responsible for the development of renal fibrosis, eventually leading to renal failure. The same CKD phenotype was observed in a mouse model with a kidney-specific G6Pase deficiency (K.G6pc-/- mice). Furthermore, GSDI patients and mice develop frequently renal cysts at late stages of the nephropathy, classifying GSDI as a potential polycystic kidney disease (PKD). PKDs are genetic disorders characterized by multiple renal cyst formation, frequently caused by the loss of expression of polycystic kidney genes, such as PKD1/2 and PKHD1. Interestingly, these genes are deregulated in K.G6pc-/- kidneys, suggesting their possible role in GSDI cystogenesis. Finally, renal cysts are known to predispose to renal malignancy development. In addition, HNF1B loss is a malignancy prediction factor. Interestingly, Hnf1b expression was decreased in K.G6pc-/- kidneys. While a single case of renal cancer has been reported in a GSDI patient, a clear cell renal carcinoma was recently observed in one K.G6pc-/- mouse (out of 36 studied mice) at a later stage of the disease. This finding highlights the need to further analyze renal cyst development in GSDI patients in order to evaluate the possible associated risk of carcinogenesis, even if the risk might be limited.
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PMID:Polycystic kidney features of the renal pathology in glycogen storage disease type I: possible evolution to renal neoplasia. 2986 65