Postnatal expression of KLF12 in the inner medullary collecting ducts of kidney and its trans-activation of UT-A1 urea transporter promoter

Maturation of the inner medulla of the kidney occurs after birth and is vital for mammals to acquire maximal urinary concentrating ability. During this process, expression of several kidney transporters and channels involved in urine concentrating mechanisms is known to be regulated. We previously isolated KLF15 as a transcription factor that regulates the expression of the ClC-K1 chloride channel. We have now found that another KLF transcription factor, KLF12, is expressed in the kidney from around 15 days after birth. To gain insight into its involvement in the maturation process of the inner medulla, we first determined the expression site of KLF12 within the kidney by in situ hybridization. By comparing the AQP2 immunolocalization in sequential sections, KLF12 was found to be expressed in the collecting ducts. Because expression of the urea transporter UT-A1 and amiloride-sensitive epithelial sodium channels ENaC is known to be tightly regulated in the collecting ducts after birth, we tested whether KLF12 has a regulatory role in the promoter activities of these genes. KLF12 is able to increase UT-A1 but not ENaC promoter activity through the binding to CACCC motif. These results suggest that KLF12 is involved in the maturation processes of collecting ducts after birth, and that UT-A1 is a target gene of KLF12.