HDAC7 is Downregulated in Bladder Tissue from Type 1 Diabetic Mice: A Potential Therapeutic Target for Diabetes‐Related Bladder Complications
Authors: Hazari Arham Syed , Carrillo‐Sepulveda Maria Alicia 
Published: June 2021

Over 50% of Type 1 Diabetes Mellitus (T1DM) patients face urologic complications including urinary bladder dysfunction. This is characterized by urinary urgency, frequency, and incontinence. The paucity of knowledge in the underlying mechanisms of diabetic bladder dysfunction indicates that new research initiatives are urgently needed. Recent studies from our lab have found that global lysine acetylation, a stable posttranslational modification, is strikingly increased in the cardiovascular tissue of diabetic rodents. Thus, we hypothesized that levels of global lysine acetylation are also altered in the bladder from T1DM and this may be linked to diabetic bladder dysfunction. To test our hypothesis, we utilized streptozotocin (STZ)‐induced diabetes, a well‐established model of T1DM. Adult male C57BL mice were randomized in two groups: Diabetic Group received 100 mg/Kg of STZ and Control Group received equal volume of vehicle via intraperitoneal injections. After 12 weeks, a diabetic state was confirmed by elevated levels of fasting blood glucose and hemoglobin A1C (310 ± 23.5 vs. 131 ± 21.21 mg/dL control, p<0.05) and (HbA1C: 7.95±0.8 vs. 5.5±0.4 % control, p<0.01), respectively. Mice were then euthanized under isoflurane (via nasal 5% in 100% O2) and bladders were isolated for molecular analysis. Increased expression of NF‐kB, a classic inflammatory marker, in the bladders from diabetic mice confirmed an inflammatory state (2.1 ± 0.1 fold increase vs. control, p<0.01, n=5). Bladders from the diabetic group exhibited 1.5 fold increase in global lysine acetylation in comparison to the control group (p<0.05, n=5). More importantly, most of the acetylated bladder proteins from the diabetic mice were found in the range of 37 to 100KDa. Since NF‐kB (65 KDa) falls in this range, we can infer that NF‐kB may be one of the proteins acetylated in diabetes. Next, we investigated whether downregulation of deacetylases (HDAC), enzymes that remove the acetyl groups from the lysine residues, was involved in the increased levels of lysine acetylation in the diabetic bladder. We found that HDCA7 expression was significantly decreased in the diabetic bladders in comparison to the controls (80% reduction vs. control, p<0.05). Our results suggest that downregulation of HDAC7 may contribute to increased global lysine acetylation in diabetic bladders. Considering that lysine acetylation of an inflammatory transcriptional factor such as NF‐kB (65KDa) leads to its activation, we will further this investigation to determine whether overexpression of deacetylases ameliorates bladder function in diabetes. Molecular approaches to overexpress HDAC7 in the bladder will be used to further confirm the role of HDAC7 in diabetes‐related bladder complications.

Support or Funding Information

In‐house Grant NYIT

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.