Fibroblast growth factor and kidney disease: Updates for emerging novel therapeutics

Abstract

The discovery of fibroblast growth factors (FGFs) and fibroblast growth factor receptors (FGFRs) provided a profound new insight into physiological and metabolic functions. FGF has a large family by having divergent structural elements and enable functional divergence and specification. FGF and FGFRs are highly expressed during kidney development. Signals from the ureteric bud regulate morphogenesis, nephrogenesis, and nephron progenitor survival. Thus, FGF signaling plays an important role in kidney progenitor cell aggregation at the sites of new nephron formation. This review will summarize the current knowledge about functions of FGF signaling in kidney development and their ability to promote regeneration in injured kidneys and its use as a biomarker and therapeutic target in kidney diseases.Further studies are essential to determine the predictive significance of the various FGF/FGFR deviations and to integrate them into clinical algorithms.

New developments in the biology of fibroblast growth factors

“…FGF signaling is required at multiple stages of kidney development from Wolffian (nephric) duct (WD) development through nephrogenesis (Krause et al, 2015; McMahon, 2016; Okazawa et al, 2015; Trivedi & Kumar, 2021; Walker et al, 2016). In the chicken, developing WD tubular elongation and lumen formation (epithelialization) proceed simultaneously in a spatiotemporally coordinated manner.…”

“…Ischemia–reperfusion (IR) injury is a major cause of acute kidney injury (AKI). FGFs have been proposed as biomarkers for AKI and as potential therapeutic targets (Deng et al, 2020; Trivedi & Kumar, 2021). In AKI, circulating levels of FGF23 are dramatically increased (discussed below) (Bar et al, 2019; Christov et al, 2019).…”

“…Treatment with FGF21 improved pancreatic fibrogenesis in CP via activation of the mTOR pathway (N. Wang, Zhao, et al, 2019). (Krause et al, 2015;McMahon, 2016;Okazawa et al, 2015;Trivedi & Kumar, 2021;Walker et al, 2016). In the chicken, developing WD tubular elongation and lumen formation (epithelialization) proceed simultaneously in a spatiotemporally coordinated manner.…”

Renal Tubular Epithelium in the Development of Renal Cell Carcinoma

“…Dysregulated FGF signaling in RCC may lead to sustained cell proliferation, contributing to increased tumor growth and progression. The in uence of FGF signaling on angiogenesis further contributes to the pathologic state in RCC, potentially supporting tumor vascularization and growth[174]. FGF signaling's role in suppressing Epithelial-Mesenchymal Transition (EMT) during development becomes dysregulated in RCC, possibly leading to a more invasive and mesenchymal phenotype in tumor cells.…”