Automated image analysis of a glomerular injury marker desmin in spontaneously diabetic Torii rats treated with losartan.
Diabetic nephropathy is a major complication in diabetes and a leading cause of end-stage renal failure. Glomerular podocytes are functionally and structurally injured early in diabetic nephropathy. A non-obese type 2 diabetes model, the spontaneously diabetic Torii (SDT) rat, is of increasing preclinical interest because of its pathophysiological similarities to human type 2 diabetic complications including diabetic nephropathy. However, podocyte injury in SDT rat glomeruli and the effect of angiotensin II receptor blocker treatment in the early stage have not been reported in detail. Therefore, we have evaluated early stages of glomerular podocyte damage and the beneficial effect of early treatment with losartan in SDT rats using desmin as a sensitive podocyte injury marker. Moreover, we have developed an automated, computational glomerulus recognition method and illustrated its specific application for quantitatively studying glomerular desmin immunoreactivity. This state-of-the-art method enabled automatic recognition and quantification of glomerular desmin-positive areas, eliminating the need to laboriously trace glomerulus borders by hand. The image analysis method not only enabled assessment of a large number of glomeruli, but also clearly demonstrated that glomerular injury was more severe in the juxtamedullary region than in the superficial cortex region. This applied not only in SDT rat diabetic nephropathy but also in puromycin aminonucleoside-induced nephropathy, which was also studied. The proposed glomerulus image analysis method combined with desmin immunohistochemistry should facilitate evaluations in preclinical drug efficacy studies as well as elucidation of the pathophysiology of diabetic nephropathy.
Safety Research LaboratoriesAdvanced Medical Research LaboratoriesResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, JapanFaculty of Science and EngineeringGunma University, Kiryu-shi, Gunma 376-8515, JapanPharmacology Research Laboratories IIResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan Kakimoto.Tetsuhiro@mf.mt-pharma.co.jp.
Tetsuhiro
T
Kakimoto
Safety Research LaboratoriesAdvanced Medical Research LaboratoriesResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, JapanFaculty of Science and EngineeringGunma University, Kiryu-shi, Gunma 376-8515, JapanPharmacology Research Laboratories IIResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan.
Kinya
K
Okada
Safety Research LaboratoriesAdvanced Medical Research LaboratoriesResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, JapanFaculty of Science and EngineeringGunma University, Kiryu-shi, Gunma 376-8515, JapanPharmacology Research Laboratories IIResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan.
Yoshihiro
Y
Hirohashi
Safety Research LaboratoriesAdvanced Medical Research LaboratoriesResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, JapanFaculty of Science and EngineeringGunma University, Kiryu-shi, Gunma 376-8515, JapanPharmacology Research Laboratories IIResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan.
Raissa
R
Relator
Safety Research LaboratoriesAdvanced Medical Research LaboratoriesResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, JapanFaculty of Science and EngineeringGunma University, Kiryu-shi, Gunma 376-8515, JapanPharmacology Research Laboratories IIResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan.
Mizue
M
Kawai
Safety Research LaboratoriesAdvanced Medical Research LaboratoriesResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, JapanFaculty of Science and EngineeringGunma University, Kiryu-shi, Gunma 376-8515, JapanPharmacology Research Laboratories IIResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan.
Taku
T
Iguchi
Safety Research LaboratoriesAdvanced Medical Research LaboratoriesResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, JapanFaculty of Science and EngineeringGunma University, Kiryu-shi, Gunma 376-8515, JapanPharmacology Research Laboratories IIResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan.
Keisuke
K
Fujitaka
Safety Research LaboratoriesAdvanced Medical Research LaboratoriesResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, JapanFaculty of Science and EngineeringGunma University, Kiryu-shi, Gunma 376-8515, JapanPharmacology Research Laboratories IIResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan.
Masashi
M
Nishio
Safety Research LaboratoriesAdvanced Medical Research LaboratoriesResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, JapanFaculty of Science and EngineeringGunma University, Kiryu-shi, Gunma 376-8515, JapanPharmacology Research Laboratories IIResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan.
Tsuyoshi
T
Kato
Safety Research LaboratoriesAdvanced Medical Research LaboratoriesResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, JapanFaculty of Science and EngineeringGunma University, Kiryu-shi, Gunma 376-8515, JapanPharmacology Research Laboratories IIResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan.
Atsushi
A
Fukunari
Safety Research LaboratoriesAdvanced Medical Research LaboratoriesResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, JapanFaculty of Science and EngineeringGunma University, Kiryu-shi, Gunma 376-8515, JapanPharmacology Research Laboratories IIResearch Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan.
Hiroyuki
H
Utsumi
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003893:Desmin / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D007091:Image Processing, Computer-Assisted; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley
D047228:Angiotensin II Type 1 Receptor Blockers; D015415:Biomarkers; D001786:Blood Glucose; D003893:Desmin; D019808:Losartan
SDT rat; automated image analysis; desmin; glomerulus; juxtamedullary glomeruli; superficial glomeruli