LIM homeobox transcription factor 1B expression affects renal interstitial fibrosis and apoptosis in unilateral ureteral obstructed rats.

Abstract

LIM homeobox transcription factor 1B (LMX1B) is a transcription factor of the LIM homeodomain type and has been implicated in the development of diverse structures such as limbs, kidneys, eyes, and the brain. Furthermore, LMX1B has been implicated in nail-patella syndrome, which is predominantly characterized by malformation of limbs and nails, and in 30% of patients, nephropathy, including renal fibrosis, is observed. Since no reports were available that studied the link between LMX1B expression and renal interstitial fibrosis, we explored if LMX1B affects typical markers of fibrosis, e.g., extracellular matrix components, profibrotic factors, and apoptosis as the final detrimental consequence. We recently showed that LMX1B acts as a negative regulator of transforming growth factor-βl, collagen type III, fibronectin, cleaved caspase-3, and the cell apoptosis rate in a renal tubular epithelial cell system under hypoxic conditions. Here, we confirmed these results in unilateral ureteral obstructed rats. Furthermore, LMX1B was distinctly expressed throughout the glomerulus and tubule lining, including epithelial cells. Knockdown of LMX1B aggravated the expression of fibrosis markers, oxidative stress, and apoptosis compared with the already increased levels due to unilateral ureteral obstruction, whereas overexpression attenuated these effects. In conclusion, reduced LMX1B levels clearly represent a risk factor for renal fibrosis, whereas overexpression affords some level of protection. In general, LMX1B may be considered to be a negative regulator of the fibrosis index, transforming growth factor-βl, collagen type III, fibronectin, cleaved caspase-3, cell apoptosis, ROS, and malondialdehyde (r = -0.756, -0.698, -0.921, -0.923, -0.843, -0.794, -0.883, and -0.825, all P < 0.01).