TY - JOUR
T1 - Renal dysfunction aggravated impaired cutaneous wound healing in diabetic mice
AU - Xie, Ping
AU - Young, Mimi Wu
AU - Bian, Huining
AU - Niknam-Bienia, Solmaz
AU - Hong, Seok
AU - Mustoe, Thomas A.
AU - Galiano, Robert D.
N1 - Publisher Copyright:
© 2018 by the Wound Healing Society
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Renal dysfunction has been associated with poor outcomes of wound healing in the diabetic population. The purpose of this study was to create an excisional wound healing model in diabetic mice with renal dysfunction to investigate the combined effects of diabetes and nephropathy on cutaneous ulcers. Renal impairment was introduced in diabetic db/db mice through unilateral nephrectomy and electrocoagulation of the contralateral kidney. Renal function was subsequently monitored with assays of blood urea nitrogen and spot urinary protein/creatinine ratio. After 8 weeks, splinted, full-thickness excisional wounds were created on the dorsal skin and harvested on postoperative days 7 and 14 for further evaluation of wound healing. Renal injury promoted the increase of blood urea nitrogen 3 weeks after initial operation, which was maintained at double the control level throughout the study, concomitantly leading to a significant increase of spot urinary protein excretion. Diabetic mice with renal injury displayed notably impaired wound healing processes, concurrent with reductions in cellular proliferation and angiogenesis, as well as increases in M1 polarized macrophages, infiltrated neutrophils, oxidative stress, and cellular apoptosis. Furthermore, quantitative polymerase chain reaction (qPCR) results displayed corresponding changes of related genes (TNF-α, IL-1β, SOD2) in the wounds of renal injured db/db mice. Renal manipulation in this study accelerated the progress of renal impairment, which was demonstrated to aggravate impaired cutaneous wound healing in diabetic mice.
AB - Renal dysfunction has been associated with poor outcomes of wound healing in the diabetic population. The purpose of this study was to create an excisional wound healing model in diabetic mice with renal dysfunction to investigate the combined effects of diabetes and nephropathy on cutaneous ulcers. Renal impairment was introduced in diabetic db/db mice through unilateral nephrectomy and electrocoagulation of the contralateral kidney. Renal function was subsequently monitored with assays of blood urea nitrogen and spot urinary protein/creatinine ratio. After 8 weeks, splinted, full-thickness excisional wounds were created on the dorsal skin and harvested on postoperative days 7 and 14 for further evaluation of wound healing. Renal injury promoted the increase of blood urea nitrogen 3 weeks after initial operation, which was maintained at double the control level throughout the study, concomitantly leading to a significant increase of spot urinary protein excretion. Diabetic mice with renal injury displayed notably impaired wound healing processes, concurrent with reductions in cellular proliferation and angiogenesis, as well as increases in M1 polarized macrophages, infiltrated neutrophils, oxidative stress, and cellular apoptosis. Furthermore, quantitative polymerase chain reaction (qPCR) results displayed corresponding changes of related genes (TNF-α, IL-1β, SOD2) in the wounds of renal injured db/db mice. Renal manipulation in this study accelerated the progress of renal impairment, which was demonstrated to aggravate impaired cutaneous wound healing in diabetic mice.
UR - http://www.scopus.com/inward/record.url?scp=85058029673&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058029673&partnerID=8YFLogxK
U2 - 10.1111/wrr.12682
DO - 10.1111/wrr.12682
M3 - Article
C2 - 30362661
AN - SCOPUS:85058029673
SN - 1067-1927
VL - 27
SP - 49
EP - 58
JO - Wound Repair and Regeneration
JF - Wound Repair and Regeneration
IS - 1
ER -