transforming-growth-factor-beta and Nephrolithiasis

SUMOylation of proteins is an important regulatory element in modulating protein function and has been implicated in the pathogenesis of numerous human diseases such as cancers, neurodegenerative diseases, brain injuries, diabetes, and familial dilated cardiomyopathy. Growing evidence has pointed to a significant role of SUMO in kidney diseases such as DN, RCC, nephritis, AKI, hypertonic stress and nephrolithiasis. Recently, emerging studies in podocytes demonstrated that SUMO might have a protective role against podocyte apoptosis. However, the SUMO code responsible for beneficial outcome in the kidney remains to be decrypted. Our recent experiments have revealed that the expression of both SUMO and SUMOylated proteins is appreciably elevated in hypoxia-induced tubular epithelial cells (TECs) as well as in the unilateral ureteric obstruction (UUO) mouse model, suggesting a role of SUMO in TECs injury and renal fibrosis. In this review, we attempt to decipher the SUMO code in the development of kidney diseases by summarizing the defined function of SUMO and looking forward to the potential role of SUMO in kidney diseases, especially in the pathology of renal fibrosis and CKD, with the goal of developing strategies that maximize correct interpretation in clinical therapy and prognosis.

Topics: Acute Kidney Injury; Apoptosis; Carcinoma, Renal Cell; Diabetic Nephropathies; Fibrosis; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Kidney Neoplasms; Nephritis; Nephrolithiasis; Podocytes; Protein Processing, Post-Translational; Smad Proteins; Small Ubiquitin-Related Modifier Proteins; Sumoylation; Transforming Growth Factor beta; Ureteral Obstruction

Nephrolithiasis is a major public health problem worldwide and Fu-Fang-Jin-Qian-Cao granules (FFJQC) is a traditional Chinese herbal formula that is used to treat nephrolithiasis. The main component of nephrolithiasis is calcium oxalate (CaOx) and the epithelial-mesenchymal transition (EMT) shown to play a crucial role in CaOx-induced kidney injury. However, the mechanism underlying the therapeutic effect of FFJQC on the CaOx-induced renal EMT is unknown.. This study explores the therapeutic benefits and mechanism of FFJQC in oxalate-induced kidney injury.. 60 male C57BL/6 mice were used in this experiment and divided into 6 groups. A mouse kidney stone model was created by intraperitoneal injection of glyoxylate at a dose of 100 mg/kg for 6 days. The standardized FFJQC was used to treat mouse crystal kidney injury by gavage at 1.35 and 2.7 g/kg, respectively. Western blotting and immunostaining for E-cadherin, cytokeratin 18 (CK18), vimentin, smooth muscle α-actin (α-SMA) and transforming growth factor β (TGF-β)/Smad pathway were conducted on renal tissues.. Following CaOx-induced kidney injury, the levels of E-cadherin and CK18 in kidney decreased, while vimentin and α-SMA levels increased. The FFJQC treatment increased the levels of E-cadherin and CK18 and decreased vimentin and α-SMA levels in varying degrees. What's more, the FFJQC reduced the expression of CaOx-induced fibrosis marker collagen II.. FFJQC alleviated the CaOx-induced renal EMT and fibrosis by regulating TGF-β/smad pathway. Therefore, the FFJQC is an important traditional Chinese medicine for the treatment of CaOx-induced renal injury and fibrosis.

Topics: Animals; Cadherins; Calcium Oxalate; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Epithelial-Mesenchymal Transition; Kidney Calculi; Male; Mice; Mice, Inbred C57BL; Nephrolithiasis; Signal Transduction; Smad Proteins; Transforming Growth Factor beta