c-JUN n-Terminal Kinase (JNK) Signaling in Autosomal Dominant Polycystic Kidney Disease

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disorder characterized by slow-growing, fluid-filled cysts in both kidneys. Liver and pancreatic cysts as well as cardiac and vascular abnormalities variably occur [1,2]. ADPKD symptoms include hypertension, kidney pain, hematuria, cyst infection, and urinary tract infections [1]. Over time, deteriorating kidney function leads to end stage renal disease (ESRD). While most ADPKD patients progress to ESRD by age 70, many reach it at younger ages [3]. Despite recent advances in therapy, ADPKD remains incurable, and for most patients treatment is limited to symptom management [4]. For patients with ESRD, renal replacement therapy in the form of dialysis or transplant is inevitable. Unfortunately, renal transplantation does not cure ESRD and patients commonly experience acute rejection, cardiovascular diseases, infection, and malignancy [5].

The Role of the Dysregulated JNK Signaling Pathway in the Pathogenesis of Human Diseases and Its Potential Therapeutic Strategies: A Comprehensive Review

“…Polycystic kidney disease (PKD) is a degenerative kidney disease wherein the renal tubules are filled with multiple fluid-filled cysts [198]. Autosomal dominant polycystic kidney disease (ADPKD) is one kind of PKD.…”

“…ADPKD has been shown to be caused by mutations of the polycystin-1 (Pkd1) and Pkd2 genes. Smith et al recently found that the JNK pathway is involved in ADPKD as inhibition of JNK activity reduces cyst growth [198].…”

“…In this review, we take several classic JNK inhibitors as examples to elucidate the application of these inhibitors in treating human diseases. and acute inflammatory insult [27,68,190,191,200] IB1/2 Type 2 diabetes [190,193] Natural phytochemicals C66 Diabetes; aortic damage; and atherosclerosis [27,[201][202][203] Lupeol Neuroinflammation; diabetes; and lipid metabolism [198,199] Gingerol Lipid metabolism [200]…”