LIM homeobox transcription factor 1B expression affects renal interstitial fibrosis and apoptosis in unilateral ureteral obstructed rats.
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).
Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; a126tianbiao@126.com.
Tian-Biao
TB
Zhou
Department of Clinical Laboratory, The Affiliated Tumor Hospital of Guangxi Medical University, NanNing, China;
Chao
C
Ou
Department of Pediatric Nephrology, The First Affiliated Hospital of GuangXi Medical University, NanNing, China; and.
Yuan-Han
YH
Qin
Department of Pediatric Nephrology, The First Affiliated Hospital of GuangXi Medical University, NanNing, China; and.
Feng-Ying
FY
Lei
Department of Pediatric Nephrology, The First Affiliated Hospital of GuangXi Medical University, NanNing, China; and.
Wei-Fang
WF
Huang
Cellular Stress and Ageing Program, Bionanoscience and Bio-Imaging Program, Bio&Nano-Solutions, Düsseldorf, Germany.
Gregor P C
GP
Drummen
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004195:Disease Models, Animal; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D060850:LIM-Homeodomain Proteins / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D014157:Transcription Factors / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014517:Ureteral Obstruction / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology
D015415:Biomarkers; D024061:Collagen Type III; D005353:Fibronectins; C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1
LIM homeobox transcription factor 1B; apoptosis; gene interference; renal interstitial fibrosis; reoxygenation injury; unilateral ureteral obstruction