Tubular overexpression of Gremlin in transgenic mice aggravates renal damage in diabetic nephropathy

Diabetic nephropathy (DN) is currently a leading cause of end-stage renal failure worldwide. Gremlin was identified as a gene differentially expressed in mesangial cells exposed to high glucose and in experimental diabetic kidneys. We have described that Gremlin is highly expressed in biopsies from patients with diabetic nephropathy, predominantly in areas of tubulointerstitial fibrosis. In streptozotocin (STZ)-induced experimental diabetes, Gremlin deletion using Grem1 heterozygous knockout mice or by gene silencing, ameliorates renal damage. To study the in vivo role of Gremlin in renal damage, we developed a diabetic model induced by STZ in transgenic (TG) mice expressing human Gremlin in proximal tubular epithelial cells. The albuminuria/creatinuria ratio, determined at week 20 after treatment, was significantly increased in diabetic mice but with no significant differences between transgenic (TG/STZ) and wild-type mice (WT/STZ). To assess the level of renal damage, kidney tissue was analyzed by light microscopy (periodic acid-Schiff and Masson staining), electron microscopy, and quantitative PCR. TG/STZ mice had significantly greater thickening of the glomerular basement membrane, increased mesangial matrix, and podocytopenia vs. WT/STZ. At the tubulointerstitial level, TG/STZ showed increased cell infiltration and mild interstitial fibrosis. In addition, we observed a decreased expression of podocin and overexpression of monocyte chemoattractant protein-1 and fibrotic-related markers, including transforming growth factor-β1, Col1a1, and α-smooth muscle actin. Together, these results show that TG mice overexpressing Gremlin in renal tubules develop greater glomerular and tubulointerstitial injury in response to diabetic-mediated damage and support the involvement of Gremlin in diabetic nephropathy.

Download Full-text

Dianthus superbus Improves Glomerular Fibrosis and Renal Dysfunction in Diabetic Nephropathy Model

Nutrients ◽

10.3390/nu11030553 ◽

2019 ◽

Vol 11 (3) ◽

pp. 553 ◽

Cited By ~ 5

Author(s):

Jung Yoon ◽

Ji Park ◽

Hye Kim ◽

Hong-Guang Jin ◽

Hye Kim ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Renal Dysfunction ◽

Transforming Growth Factor ◽

Mesangial Cells ◽

Periodic Acid ◽

Transforming Growth Factor Β ◽

Collagen Type Iv ◽

Model Assessment ◽

Periodic Acid Schiff ◽

Monocyte Chemoattractant Protein 1

Glomerular fibrosis is caused by an accumulation of intercellular spaces containing mesangial matrix proteins through either diffused or nodular changes. Dianthus superbus has been used in traditional medicine as a diuretic, a contraceptive, and an anti-inflammatory agent. The aim of this study was to investigate the effects of Dianthus superbus-EtOAc soluble fraction (DS-EA) on glomerular fibrosis and renal dysfunction, which has been implicated in diabetic nephropathy in human renal mesangial cells and db/db mice. DS-EA was administered to db/db mice at 10 or 50 mg/kg/day for 8 weeks. DS-EA treatment significantly ameliorated blood glucose, insulin, the homeostasis model assessment of insulin resistance (HOMA-IR) index, and HbA1c in diabetic mice. DS-EA decreased albumin excretion, creatinine clearance (Ccr), and plasma creatinine levels. DS-EA also ameliorated the levels of kidney injury molecules-1 (KIM-1) and C-reactive protein. DS-EA reduced the periodic acid-Schiff (PAS) staining intensity and basement membrane thickening in glomeruli of the diabetic nephropathy model. In addition, DS-EA suppressed transforming growth factor-β (TGF-β)/Smad signaling. Collagen type IV, a glomerular fibrosis biomarker, was significantly decreased upon DS-EA administration. DS-EA pretreatment attenuated levels of inflammation factors such as intracellular cell adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1). DS-EA inhibited the translocation of nuclear factor kappa B (NF-κB) in Angiotensin II (Ang II)-stimulated mesangial cells. These findings suggest that DS-EA has a protective effect against renal inflammation and fibrosis. Therefore, DS-EA may serve as a potential therapeutic agent targeting glomerulonephritis and glomerulosclerosis, which lead to diabetic nephropathy.

Download Full-text

Dexrazoxane Alleviated Doxorubicin-Induced Nephropathy in Rats

Pharmacology ◽

10.1159/000521220 ◽

2022 ◽

pp. 1-10

Author(s):

Huihui Hu ◽

Caipeng Xie ◽

Zeping Weng ◽

Pei Yu ◽

Yuqiang Wang ◽

...

Keyword(s):

Renal Function ◽

Transforming Growth Factor ◽

Interstitial Fibrosis ◽

Smooth Muscle Actin ◽

Periodic Acid ◽

Kidney Tissue ◽

Tunel Staining ◽

Protective Effects ◽

Renal Interstitial Fibrosis ◽

Alpha Smooth Muscle Actin

Introduction: Doxorubicin (DOX), an anthracycline antitumor agent, has been widely used against various solid tumors and hematological malignancies. However, the clinical application of DOX is restricted by its multiple organ toxicity including nephrotoxicity. This study investigated the protective effects and mechanisms of dexrazoxane (DZR) against DOX-induced nephropathy in rats. Methods: Male Sprague Dawley rats received 2.5 mg/kg DOX once a week for 5 consecutive weeks. 24-h urinary protein and renal function injury biomarkers were determined to evaluate the renal function. Histopathological changes and glomerulosclerosis were examined by hematoxylin and eosin and periodic acid-Schiff staining. The change of renal ultrastructure in the DOX-induced rats was observed by the electron microscopy. The renal apoptosis was detected by TUNEL staining and measured the protein expression of Caspase-3, Bcl-2, and Bax. Renal interstitial fibrosis was determined by Masson staining and immunohistochemistry examination. The levels of vimentin, alpha-smooth muscle actin (α-SMA), and transforming growth factor β (TGF-β) in kidney tissue were detected by Western blot. Results: DZR pretreatment markedly raised the survival rate and improved the renal dysfunction in DOX-treated rats. DZR ameliorated DOX-induced histopathological lesion of glomerular and tubular and apoptosis. DZR restored the oxidant/antioxidant balance via regulating the levels of MDA, SOD, and TAC. DZR reduced DOX-induced collagen IV deposition and renal interstitial fibrosis and downregulated the fibrosis-related protein expressions of vimentin, α-SMA, and TGF-β1. Conclusion: Our results suggest DZR exerted its protective effects against DOX-induced nephropathy through inhibition of lipid peroxidation, apoptosis, and fibrosis.

Download Full-text

Silencing of long noncoding RNA XIST protects against renal interstitial fibrosis in diabetic nephropathy via microRNA-93-5p-mediated inhibition of CDKN1A

AJP Renal Physiology ◽

10.1152/ajprenal.00254.2019 ◽

2019 ◽

Vol 317 (5) ◽

pp. F1350-F1358 ◽

Cited By ~ 6

Author(s):

Jindou Yang ◽

Yan Shen ◽

Xia Yang ◽

Yanjun Long ◽

Shuang Chen ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Molecular Mechanism ◽

High Glucose ◽

Noncoding Rna ◽

Transforming Growth Factor ◽

Interstitial Fibrosis ◽

Kidney Tissue ◽

Luciferase Reporter ◽

Renal Interstitial Fibrosis ◽

Endogenous Expression

Long noncoding RNAs (lncRNAs) have been reported to play an important role in diabetic nephropathy (DN). However, the molecular mechanism involved in this process remains poorly understood. Thus, the present study aimed to explore the function and molecular mechanism of dysregulated lncRNA X-inactive specific transcript (XIST) in DN. DN mouse models were established by streptozotocin treatment, and human renal tubular epithelial HK-2 cells were exposed to high glucose to produce an in vitro model. XIST was highly expressed in renal tissues of patients with DN, mice with DN, and high glucose-exposed HK-2 cells. To identify the interaction among XIST, miR-93-5p, and cyclin-dependent kinase inhibitor 1A (CDKN1A) and to analyze the functional significance of their interaction in renal interstitial fibrosis, we altered endogenous expression of XIST and miR-93-5p and CDKN1A. Dual-luciferase reporter assay results suggested that XIST was highly expressed in the kidney tissue of DN mice and high glucose-exposed HK-2 cells. XIST was identified to be a lncRNA that could bind to miR-93-5p, and CDKN1A was a target of miR-93-5p. Downregulated expression of XIST led to an increase in miR-93-5p expression, thereby decreasing CDKN1A and suppressing renal interstitial fibrosis in DN. Consistently, XIST knockdown reduced the expression of fibrosis markers (fibronectin, collagen type IV, and transforming growth factor-β1). Restoration of CDKN1A or decreasing miR-93-5p yielded a reversed effect on renal interstitial fibrosis. In conclusion, our study demonstrated that silenced XIST inducing miR-93-5p-dependent CDKN1A inhibition was beneficial for preventing renal interstitial fibrosis in DN, which may provide a future strategy to prevent the progression of DN.

Download Full-text

Transgenic overexpression of GLUT1 in mouse glomeruli produces renal disease resembling diabetic glomerulosclerosis

AJP Renal Physiology ◽

10.1152/ajprenal.00466.2009 ◽

2010 ◽

Vol 299 (1) ◽

pp. F99-F111 ◽

Cited By ~ 33

Author(s):

Youli Wang ◽

Kathleen Heilig ◽

Thomas Saunders ◽

Andrew Minto ◽

Dilip K. Deb ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Transforming Growth Factor ◽

Mesangial Cells ◽

Glomerular Disease ◽

Membrane Thickness ◽

Renal Tubules ◽

Glomerular Mesangial Cells ◽

Diabetic Glomerulosclerosis ◽

Basement Membrane Thickness ◽

Intracellular Glucose

Previous work identified an important role for hyperglycemia in diabetic nephropathy (The Diabetes Control and Complications Trial Research Group. N Engl J Med 329: 977–986, 1993; UK Prospective Diabetes Study Group. Lancet 352: 837–853, 1998), and increased glomerular GLUT1 has been implicated. However, the roles of GLUT1 and intracellular glucose have not been determined. Here, we developed transgenic GLUT1-overexpressing mice (GT1S) to characterize the roles of GLUT1 and intracellular glucose in the development of glomerular disease without diabetes. GLUT1 was overexpressed in glomerular mesangial cells (MC) of C57BL6 mice, a line relatively resistant to diabetic nephropathy. Blood pressure, blood glucose, glomerular morphometry, matrix proteins, cell signaling, transcription factors, and selected growth factors were examined. Kidneys of GT1S mice overexpressed GLUT1 in glomerular MCs and small vessels, rather than renal tubules. GT1S mice were neither diabetic nor hypertensive. Glomerular GLUT1, glucose uptake, mean capillary diameter, and mean glomerular volume were all increased in the GT1S mice. Moderately severe glomerulosclerosis (GS) was established by 26 wk of age in GT1S mice, with increased glomerular type IV collagen and fibronectin. Modest increases in glomerular basement membrane thickness and albuminuria were detected with podocyte foot processes largely preserved, in the absence of podocyte GLUT1 overexpression. Activation of glomerular PKC, along with increased transforming growth factor-β1, VEGFR1, VEGFR2, and VEGF were all detected in glomeruli of GT1S mice, likely contributing to GS. The transcription factor NF-κB was also activated. Overexpression of glomerular GLUT1, mimicking the diabetic GLUT1 response, produced numerous features typical of diabetic glomerular disease, without diabetes or hypertension. This suggested GLUT1 may play an important role in the development of diabetic GS.

Download Full-text

Mast cell infiltration associated with tubulointerstitial fibrosis in chronic Aristolochic Acid Nephropathy

Human & Experimental Toxicology ◽

10.1191/0960327105ht502oa ◽

2005 ◽

Vol 24 (2) ◽

pp. 41-47 ◽

Cited By ~ 6

Author(s):

Yichao Wu ◽

Zhihong Liu ◽

Weixin Hu ◽

Leishi Li

Keyword(s):

Mast Cell ◽

Aristolochic Acid ◽

Interstitial Fibrosis ◽

Smooth Muscle Actin ◽

Periodic Acid ◽

Basement Membranes ◽

Cell Infiltration ◽

Alpha Smooth Muscle Actin ◽

Periodic Acid Schiff ◽

Aristolochic Acid Nephropathy

Aristolochic Acid Nephropathy (AAN) is regarded as a kind of toxic nephropathy caused by the formation of DNA- aristolochic acid adducts in renal parenchymal cells. However, the underlying mechanisms driving the progression of renal interstitial fibrosis in AAN still remains unclear. This study aims to elucidate the role of some immunological factors, especially mast cells (MCs), in the pathogenesis of AAN. Sixteen patients with AAN were enrolled in this study, including five acute and 11 chronic AAN. Monoclonal antibodies against human tryptase, alpha smooth muscle actin (α-SMA), and CD68 were applied on serial sections, which were further counterstained with Periodic Acid-Schiff. It was found that massive tryptase-positive MCs were observed in the fibrotic areas in chronic AAN, especially around thickened tubular basement membranes where myofibroblasts accumulated too. In contrast, MCs infiltrated to a less extent in acute AAN, and were barely found in normal control kidneys. In chronic AAN, the number of MCs in the tubulointerstitium was positively correlated with the degree of renal fibrosis ( r=0.64, P<0.05), but not with serum creatinine levels. Meanwhile, the recruitment of MCs into the renal interstitium is accompanied with local proliferation of myofibroblasts. Macrophages were not abundant, neither in acute nor in chronic AAN. Our findings show for the first time that mast cell infiltration seems to be associated with the progression of fibrosis in the renal tubulointerstitium in chronic AAN.

Download Full-text

1,25-(OH)2D3 ameliorates renal interstitial fibrosis in UUO rats through the AMPKα/mTOR pathway

Journal of International Medical Research ◽

10.1177/0300060520981360 ◽

2021 ◽

Vol 49 (2) ◽

pp. 030006052098136

Author(s):

Shasha Tian ◽

Xiaopeng Yang ◽

Jianwu Wang ◽

Jing Luo ◽

Hui Guo

Keyword(s):

Transforming Growth Factor ◽

Interstitial Fibrosis ◽

Smooth Muscle Actin ◽

Kidney Tissue ◽

Signalling Pathway ◽

Sham Operation ◽

Tubular Atrophy ◽

Sham Operation Group ◽

Mtor Signalling ◽

Mtor Signalling Pathway

Objective To investigate the effects of 1,25(OH)2D3 on renal fibrosis associated with the AMP-activated protein kinase (AMPK)α/mechanistic target of rapamycin (mTOR) signalling pathway in a rat model of unilateral ureteral obstruction (UUO). Methods A total of 54 male Sprague Dawley rats were randomly divided into three groups: sham-operation group, UUO group, and UUO plus calcitriol (3 ng/100 g) group. Renal tissue was excised for histological examination by immunohistochemistry and Western blot, and for gene expression analysis using real-time polymerase chain reaction. Results 1,25(OH)2D3 enhanced AMPKα levels, inhibited mTOR levels and slowed the development of interstitial fibrosis in kidney tissue. Compared with the UUO plus calcitriol group, UUO rats demonstrated more severe renal damage characterized by marked tubular atrophy, interstitial fibrosis and significant induction of fibrogenic transforming growth factor-β1 and increased extra-cellular matrix proteins (α-smooth muscle actin and collagen type III), and decreased E-cadherin. Conclusion Treatment with 1,25(OH)2D3 altered the AMPKα/mTOR signalling pathway to suppress excessive fibroblast activation observed in UUO rats. This may serve as a novel mechanism to ameliorate renal dysfunction and fibrotic lesions.

Download Full-text

Huangqi-Danshen Decoction Ameliorates Adenine-Induced Chronic Kidney Disease by Modulating Mitochondrial Dynamics

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/9574045 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Xinhui Liu ◽

Shiying Huang ◽

Fochang Wang ◽

Lin Zheng ◽

Jiandong Lu ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Interstitial Fibrosis ◽

Mitochondrial Dynamics ◽

Smooth Muscle Actin ◽

Periodic Acid ◽

Public Health Problem ◽

High Morbidity ◽

Tubular Atrophy ◽

Periodic Acid Schiff

Chronic kidney disease (CKD) is a leading public health problem with high morbidity and mortality. However, the therapies remain limited. Traditional Chinese medicine (TCM) has been used for treating kidney disease for thousands of years and is an effective alternative treatment for CKD patients in China and other Asian countries. In the present study, we aimed to investigate the effect and mechanism of Huangqi-Danshen decoction (HDD), a TCM herbal decoction, on treating CKD. CKD rat model was induced by adding 0.75% adenine to the diet for 4 weeks. HDD extract was administrated orally to CKD rats at the dose of 4.7 g/kg/d for consecutive 4 weeks in adenine-induced CKD rats. Kidney function was evaluated by the levels of serum creatinine (Scr) and blood urea nitrogen (BUN). The pathological changes of kidney tissues were observed by periodic acid-Schiff (PAS) and Masson’s trichrome staining. The proteins expression of renal fibrosis and mitochondrial dynamics were determined and quantified by Western blot analysis. CKD rats showed obvious decline in renal function as evidenced by increased levels of Scr and BUN, which were blunted by HDD treatment. HDD could also improve tubular atrophy and interstitial fibrosis of CKD rats. Moreover, HDD downregulated fibronectin, type IV collagen, and α-smooth muscle actin expression in CKD rats. Furthermore, mitochondrial dynamics was disturbed in CKD rats, which manifested as increased mitochondrial fission and decreased mitochondrial fusion. HDD treatment restored mitochondrial dynamics in CKD rats by repressing dynamin-related protein 1 and Mid 49/51 expression, promoting mitofusin 2 expression, and suppressing optic atrophy 1 proteolysis. In conclusion, HDD could significantly retard CKD progression through modulating mitochondrial dynamics.

Download Full-text

Conversion to Sirolimus Ameliorates Cyclosporine-Induced Nephropathy in the Rat: Focus on Serum, Urine, Gene, and Protein Renal Expression Biomarkers

BioMed Research International ◽

10.1155/2014/576929 ◽

2014 ◽

Vol 2014 ◽

pp. 1-17 ◽

Cited By ~ 7

Author(s):

José Sereno ◽

Sara Nunes ◽

Paulo Rodrigues-Santos ◽

Helena Vala ◽

Petronila Rocha-Pereira ◽

...

Keyword(s):

Renal Damage ◽

Molecular Mechanisms ◽

Periodic Acid ◽

Kidney Tissue ◽

Periodic Acid Schiff ◽

Gene And Protein Expression ◽

Hematoxylin And Eosin ◽

Kidney Lesions ◽

Renal Expression ◽

Relevant Gene

Protocols of conversion from cyclosporin A (CsA) to sirolimus (SRL) have been widely used in immunotherapy after transplantation to prevent CsA-induced nephropathy, but the molecular mechanisms underlying these protocols remain nuclear. This study aimed to identify the molecular pathways and putative biomarkers of CsA-to-SRL conversion in a rat model. Four animal groups (n=6) were tested during 9 weeks: control, CsA, SRL, and conversion (CsA for 3 weeks followed by SRL for 6 weeks). Classical and emergent serum, urinary, and kidney tissue (gene and protein expression) markers were assessed. Renal lesions were analyzed in hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome stains. SRL-treated rats presented proteinuria and NGAL (serum and urinary) as the best markers of renal impairment. Short CsA treatment presented slight or even absent kidney lesions and TGF-β, NF-κβ, mTOR, PCNA, TP53, KIM-1, and CTGF as relevant gene and protein changes. Prolonged CsA exposure aggravated renal damage, without clear changes on the traditional markers, but with changes in serums TGF-βand IL-7, TBARs clearance, and kidney TGF-βand mTOR. Conversion to SRL prevented CsA-induced renal damage evolution (absent/mild grade lesions), while NGAL (serum versus urine) seems to be a feasible biomarker of CsA replacement to SRL.

Download Full-text

Conjunctival myxoid stromal tumour: a distinctive clinicopathological and immunohistochemical study

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2018-312747 ◽

2018 ◽

Vol 103 (9) ◽

pp. 1259-1265 ◽

Cited By ~ 4

Author(s):

Xiao-Yi Qin ◽

Zhe-Hao Jin ◽

You-Pei Wang ◽

Zong-Duan Zhang

Keyword(s):

Smooth Muscle Actin ◽

Periodic Acid ◽

Clinical Findings ◽

Stromal Tumour ◽

Bulbar Conjunctiva ◽

Low Grade ◽

Ki 67 ◽

Periodic Acid Schiff ◽

Multiple Spindle ◽

Immunohistochemical Stains

Background/aimsTo describe the clinicopathological and immunohistochemical characteristics of 10 patients representing a new entity of benign conjunctival myxoid stromal tumours.MethodsRetrospective review of clinical findings, histopathological and immunohistochemical studies identified 10 cases of low-grade conjunctival myxoid stromal tumours. Specimens were routinely processed and stained with H&E. Immunohistochemical stains for CD34, CD68, vimentin, S100, smooth muscle actin (SMA), myosin, desmin, actin, Bcl-2 and Ki-67 were performed. Specific stains for Alcian-blue periodic acid-Schiff (AB-PAS) and aldehyde fuchsin stains were also performed.ResultsTen patients with an average age of 45.6±11.1 years had a tender white or faint yellow to red mass on the bulbar conjunctiva. All the lesions were completely removed, and none of the patients relapsed. Histologically, all neoplasms consisted of spindle-shaped cells that showed signs of pseudonuclear inclusions, multinuclear cells and had no atypia. The stroma consisted of a large amount of mucus and was infiltrated with delicate to ropey collagens, a few mast cells and new vessels. Immunohistochemical stains were positive for CD34, vimentin and Bcl-2; partial positive for CD68; very low for Ki-67; and negative for S100, SMA, myosin, desmin and actin. AB-PAS suggested that the stroma was mucinous.ConclusionsThese rare benign mesenchymal conjunctival tumours are mostly unilateral and occur in the bulbar conjunctiva. Complete resection is the radical treatment. These lesions are characterised by multiple spindle cells, a large amount of mucus, and sharing similar basic histopathological features with conjunctival myxoma and conjunctival stromal tumour. We suggest naming these lesions ‘conjunctival myxoid stromal tumours’.

Download Full-text

Canine Cutaneous Clear Cell Adnexal Carcinoma: Histopathology, Immunohistochemistry, and Biologic Behavior of 26 Cases

Journal of Veterinary Diagnostic Investigation ◽

10.1177/104063870501700501 ◽

2005 ◽

Vol 17 (5) ◽

pp. 403-411 ◽

Cited By ~ 9

Author(s):

F. Y. Schulman ◽

T. P. Lipscomb ◽

T. J. Atkin

Keyword(s):

Clear Cell ◽

Regional Lymph Node ◽

Smooth Muscle Actin ◽

Periodic Acid ◽

Dermal Papilla ◽

Low Grade ◽

Periodic Acid Schiff ◽

Regional Lymph Nodes ◽

S 100 ◽

Clear Cytoplasm

Thirty tumors including 27 distinctive cutaneous neoplasms and 3 metastatic tumors from 26 dogs were collected from diagnostic submissions to 3 laboratories. Characteristic histopathologic features included location in the subcutis or dermis (or both); lobular, nodular, and nest-like architecture; and a component of epithelioid cells with clear cytoplasm. Additional features present in most cases included follicular dermal papilla-like structures, low mitotic index, nuclear pleomorphism, necrosis, and mineralization. Cytoplasmic periodic acid Schiff—positivity, which was abolished by pretreatment with diastase, indicated the presence of glycogen in all cases. The oil red O stain did not demonstrate cytoplasmic lipid. Melanin granules, accentuated by the Fontana-Masson method, were observed infrequently. A sparsely cellular mucinous stroma and stromal cartilaginous differentiation were uncommon. By immunohistochemistry, neoplastic cells stained positively for cytokeratin (29 of 29), vimentin (28 of 28), S-100 protein (24 of 29), and melan A (8 of 12); results were negative for smooth muscle actin and calponin in all cases. Clinical follow-up information was obtained on all 26 dogs. One tumor recurred, 1 metastasized to a regional lymph node, and 1 metastasized to regional lymph nodes twice. In another case, possible pulmonary metastasis was noted radiographically. The findings are consistent with a poorly differentiated, low-grade, adnexal carcinoma of the skin. Similar canine cutaneous neoplasms have been reported as “clear-cell hidradenocarcinoma” and “follicular stem cell carcinoma.” The authors propose the designation “cutaneous clear cell adnexal carcinoma.”

Download Full-text