**2.2 Hormones regulating the expression and function of endocytic receptors**

Angiotensin II and insulin are two major hormones involved in regulating the expression and function of megalin (Hosojima et al. 2009) (Fig. 2), but no hormones have been identified that regulate cubilin and amnionless expression.

## **2.2.1 Angiotensin II**

Angiotensin II downregulates the expression and function of megalin via the extracellularsignal-regulated kinase (ERK)1/2 signaling pathway in cultured PTCs (Hosojima et al. 2009). Intrarenal levels of angiotensin II are augmented in CKD (Kobori et al. 2007), which is involved in the development of hypertension as discussed below. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are thus likely to target the increased action of angiotensin II in the kidney. These agents may be effective in suppressing the reduced expression of megalin in CKD and in preventing proteinuria/albuminuria (Tojo et al. 2003).

Megalin also appears to regulate the intrarenal actions of angiotensin II by internalizing angiotensin II (Gonzalez-Villalobos et al. 2005) and angiotensin-(1-7) (Gonzalez-Villalobos et al. 2006), as well as mediating the endocytosis of angiotensinogen that is filtered by glomeruli (Pohl et al. 2010).
