Review Article

Proximal Tubule Cell Hypothesis for Cardiorenal Syndrome in Diabetes

Figure 1

Normal functions of proximal tubule cells (PTCs) and structural changes around the cells in the early stages of diabetic nephropathy. Normal functions of PTCs include (1) reabsorption and intracellular processing of glomerular-filtered substances via apical membrane receptors, transporters, and channels; (2) uptake of substances via basolateral membrane transporters followed by metabolism or secretion into the urinary space; (3) synthesis of bioactive substances that are released to peritubular capillaries. These functions are impaired in diabetic nephropathy even at the early stages in which PTCs are hypertrophied with increased metabolic demands and are phenotypically altered. In addition, tubular basement membranes (TBMs) are thickened, and interstitial spaces are expanded with fibrosis, alienating PTCs from interacting with peritubular capillaries.
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