SMAD3 and diabetic kidney disease: In kidney injury in vivo, SIS3 delayed the development of diabetic nephropathy in streptozotocin-induced type 1 diabetic mice and type 2 diabetic db/db mice, and the inhibition of Smad3 in SIS3-treated db/db mouse kidneys was associated with increased Smad7 expression and suppression of NF-κB-mediated inflammation 82, 175.