Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Am J Physiol Renal Physiol. 2013 Aug 1;305(3):F295-303. doi: 10.1152/ajprenal.00527.2012. Epub 2013 May 29.
Telomeres are protective structures at the ends of chromosomes that have important implications for aging. To address the question of whether telomeres contribute to feline chronic kidney disease (CKD), we evaluated kidney, liver, and skin samples from 12 cats with naturally occurring CKD, 12 young normal cats, and 6 old normal cats. Telomere length was assessed using standard telomere fluorescent in situ hybridization (TEL-FISH) combined with immunohistochemistry (TELI-FISH) to identify proximal (PTEC) and distal tubular epithelial cells (DTEC), whereas senescence-associated β-galactosidase (SABG) staining was used to evaluate senescence. Results revealed statistically significant decreases in the average telomere fluorescence intensity (TFI) of PTEC in CKD cats compared with young and geriatric normal cats, and in the DTEC of CKD cats compared with young normal cats. When histograms of individual TFI were compared, statistically significant decreases in the PTEC and DTEC of CKD cats were observed compared with young and geriatric normal cats. Concomitantly, a statistically significant increase in SABG staining was seen in CKD kidney samples compared with young normal cats. CKD cats tended to have increased SABG staining in the kidney compared with normal geriatric cats, but this did not reach statistical significance. No significant telomere shortening in liver or skin from any group was observed. Real-time quantitative telomeric repeat amplification protocol assessment of renal telomerase activity revealed comparable low levels of telomerase activity in all groups. Our results suggest that shortened telomeres and increased senescence in the kidneys of CKD cats may represent novel targets for interventional therapy.
端粒是染色体末端的保护性结构，对衰老有重要影响。为了研究端粒是否与猫慢性肾病（CKD）有关，我们评估了 12 只自然发生 CKD 的猫、12 只年轻正常猫和 6 只老年正常猫的肾脏、肝脏和皮肤样本。使用标准的端粒荧光原位杂交（TEL-FISH）结合免疫组织化学（TELI-FISH）评估端粒长度，以识别近端（PTEC）和远端肾小管上皮细胞（DTEC），而衰老相关β-半乳糖苷酶（SABG）染色用于评估衰老。结果显示，与年轻和老年正常猫相比，CKD 猫的 PTEC 平均端粒荧光强度（TFI）显著降低，CKD 猫的 DTEC 与年轻正常猫相比也显著降低。当比较个体 TFI 的直方图时，与年轻和老年正常猫相比，CKD 猫的 PTEC 和 DTEC 均显著降低。同时，与年轻正常猫相比，CKD 肾脏样本中的 SABG 染色明显增加。与老年正常猫相比，CKD 猫的肾脏中 SABG 染色增加，但无统计学意义。未观察到任何组的肝脏或皮肤中端粒明显缩短。对所有组的肾脏端粒酶活性进行实时定量端粒重复扩增协议评估显示，端粒酶活性水平相当低。我们的结果表明，CKD 猫肾脏中端粒缩短和衰老增加可能代表干预治疗的新靶点。
