LEP and kidney disorder: Furthermore, due to its role in signaling molecule degradation, megalin expression is required to negatively regulate the signaling of molecules involved in the early and late stages of renal disease, including angiotensin II [23] and leptin [22]; in addition to their other functions, these signaling molecules are involved in the regulation of renal inflammation and fibrosis and, for example, can induce the expression of TGFβ and Smad 2/3 activation [80], [81], [82], [83].