RGD Reference Report - p38 MAPK and MAPK kinase 3/6 mRNA and activities are increased in early diabetic glomeruli. - Rat Genome Database

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p38 MAPK and MAPK kinase 3/6 mRNA and activities are increased in early diabetic glomeruli.

Authors: Kang, SW  Adler, SG  Lapage, J  Natarajan, R 
Citation: Kang SW, etal., Kidney Int. 2001 Aug;60(2):543-52.
RGD ID: 7495813
Pubmed: PMID:11473637   (View Abstract at PubMed)
DOI: DOI:10.1046/j.1523-1755.2001.060002543.x   (Journal Full-text)

BACKGROUND: The p38 mitogen-activated protein kinase (MAPK) pathway is activated by several stress factors, potentially leading to cellular apoptosis and growth. Little is known about the pattern of glomerular p38 MAPK pathway activation during the course of diabetic nephropathy (DN). We examined the activity and expression of the p38 MAPK pathway members, p38 MAPK, MKK3/6, cAMP-responsive element binding protein (CREB), and MAPK phosphatase-1 (MKP-1), in experimental DN in rats over the course of four months. METHODS: Control (C; N = 16) and diabetic (DM; N = 16) rats were studied. Four rats from each group were sacrificed monthly, and competitive reverse transcription-polymerase chain reaction and Western blot were performed with microdissected and sieved glomeruli, respectively. RESULTS: Glomerular p38 MAPK mRNA expression was significantly higher in DM than C (P < 0.01) throughout the four-month period. Western blot revealed an average 3.1-fold increase in p38 MAPK protein throughout the study period (P < 0.05). However, p38 MAPK activity was significantly increased only in one- and two-month diabetic glomeruli. Glomerular MKK3/6 and CREB mRNA as well as activity were significantly increased only in one- and two-month DM compared with C. MKP-1 mRNA showed a similar pattern. CONCLUSIONS: Glomerular p38 MAPK activity was increased in early DN. Parallel to this, we also showed, to our knowledge for the first time, that there were increased MKK3/6 and CREB activities and mRNA expression. This activated p38 MAPK pathway in diabetic glomeruli may, in part, play a role in the pathogenesis of early hypertrophy and extracellular matrix accumulation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  ISOMap2k3 (Rattus norvegicus)7495813; 7495813mRNA:increased expression:kidney and glomerulusRGD 
Experimental Diabetes Mellitus  ISOMap2k6 (Rattus norvegicus)7495813; 7495813mRNA:increased expression:kidney and glomerulusRGD 
Experimental Diabetes Mellitus  IEP 7495813; 7495813mRNA:increased expression:kidney and glomerulusRGD 

Objects Annotated

Genes (Rattus norvegicus)
Map2k3  (mitogen activated protein kinase kinase 3)
Map2k6  (mitogen-activated protein kinase kinase 6)

Genes (Mus musculus)
Map2k3  (mitogen-activated protein kinase kinase 3)
Map2k6  (mitogen-activated protein kinase kinase 6)

Genes (Homo sapiens)
MAP2K3  (mitogen-activated protein kinase kinase 3)
MAP2K6  (mitogen-activated protein kinase kinase 6)


Additional Information