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Simple Summary: The mechanisms of renal cell carcinoma (RCC) progression are not well understood. There is a need to develop effective therapies against metastatic disease and to reduce high disease prevalence among minority and male populations. Here, we detail limited but compelling evidence for the role of the Hippo-YAP (Yes-associated protein)/TAZ (transcriptional coactivator with PDZ-binding motif) pathway in RCC progression. YAP/TAZ activation is evident in human RCC. Inhibition of YAP/TAZ in mice with kidney cancer mitigates neoplastic behavior, highlighting the therapeutic benefit of YAP/TAZ targeting in RCC. This review also summarizes, for the first time, upstream controls and oncogenic consequences associated with Hippo-YAP/TAZ dysregulation in progressive RCC. We describe critical literature gaps and future studies necessary to position the Hippo pathway among well-established drivers of kidney cancer progression. Although Hippo-YAP/TAZ pathway involvement has been extensively studied in the development of certain cancers, the involvement of this cascade in kidney cancer progression is not well-established and, therefore, will be the focus of this review. Renal cell carcinoma (RCC), the most prevalent kidney tumor subtype, has a poor prognosis and a high mortality rate. Core Hippo signaling inactivation (e.g., LATS kinases) leads to the nuclear translocation of YAP/TAZ where they bind to co-transcriptional factors such as TEAD promoting transcription of genes which initiates various fibrotic and neoplastic diseases. Loss of expression of LATS1/2 kinase and activation of YAP/TAZ correlates with poor survival in RCC patients. Renal-specific ablation of LATS1 in mice leads to the spontaneous development of several subtypes of RCC in a YAP/TAZ-dependent manner. Genetic and pharmacological inactivation of YAP/TAZ reverses the oncogenic potential in LATS1-deficient mice, highlighting the therapeutic benefit of network targeting in RCC. Here, we explore the unique upstream controls and downstream consequences of the Hippo-YAP/TAZ pathway deregulation in renal cancer. This review critically evaluates the current literature on the role of the Hippo pathway in RCC progression and highlights the recent scientific evidence designating YAP/TAZ as novel therapeutic targets against kidney cancer. [ABSTRACT FROM AUTHOR]

Background: Diabetic kidney disease (DKD) is a common disorder with multiple serious clinical implications, including an increased risk of end-stage kidney disease (ESKD), cardiovascular complications, heart failure, onset or worsening of hypertension, and premature death. Patients with DKD frequently require dialysis or kidney transplantation to manage their ESKD. Summary: Upregulation of the renin-angiotensin-aldosterone system is an important contributor to kidney disease progression, as highlighted by the results of trials evaluating angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with albuminuria. Increasing evidence suggests the existence of a multidirectional network that involves aldosterone, the mineralocorticoid receptor (MR), and the Ras-related C3 botulinum toxin substrate 1 (Rac1) as driving forces in the generation of reactive oxygen species and oxidative stress-induced injury in the initiation of interstitial nephritis and eventual fibrosis in chronic kidney disease and DKD. The MR is a key element of this triangle, as highlighted by the beneficial effect of MR antagonists in preventing or reducing aldosterone- or Rac1-related effects in basic science studies, and the improved patient outcomes observed in clinical studies. Key Messages: Aldosterone can promote kidney disease in diabetes via the MR and via MR-independent actions through Rac1. However, the MR remains a key element of this triangle, with clinical data supporting the use of MR antagonists in delaying the progression of kidney disease in diabetes. [ABSTRACT FROM AUTHOR]

Mammalian kidneys consist of more than 30 different types of cells. A challenging task is to identify and characterize the stem/ progenitor subpopulations that establish the lineage relationships among these cellular elements during nephrogenesis in the embryonic and neonate kidneys and during tissue homeostasis and/or injury repair in the mature kidney. Moreover, the potential clinical utility of stem/progenitor cells holds promise for the development of new regenerative medicine approaches for the treatment of renal diseases. Stem cells are defined by unlimited self-renewal capacity and pluripotentiality. Progenitor cells have pluripotentiality but no or limited self-renewal potential. Cre-LoxP-based in vivo genetic lineage tracing is a powerful tool to identify stem/progenitor cells in their native environment. Hypothetically, this technique enables investigators to accurately track the progeny of a single cell or a group of cells. The Cre/LoxP system has been widely used to uncover the function of genes in various mammalian tissues and to identify stem/progenitor cells through in vivo lineage tracing analyses. In this review, we summarize the recent advances in the development and characterization of various Cre drivers and their use in identifying potential renal stem/progenitor cells in both developing and mature mouse kidneys. [ABSTRACT FROM AUTHOR]