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ERK5 activation enhances mesangial cell viability and collagen matrix accumulation in rat progressive glomerulonephritis.
Am J Physiol Renal Physiol. 2010 Jan; 298(1):F167-76.AJ

Abstract

The mitogen-activated protein kinase (MAPK) cascade plays an important role in the regulation of various cellular functions in glomerulonephritis (GN). Here, we investigated whether extracellular signal-regulated kinase 5 (ERK5), a member of the MAPK family, is involved in the pathogenesis of chronic mesangioproliferative GN, using a rat model induced by uninephrectomy and anti-Thy-1 antibody injection. Immunostaining of kidneys obtained at different time points revealed that phospho-ERK5 was weakly expressed in control glomeruli but dramatically increased in a typical mesangial pattern after 28 and 56 days of GN. A semiquantitative assessment indicated that glomerular phospho-ERK5 expression closely paralleled the accumulation of extracellular matrix (ECM), collagen type I, as well as glomerular expression of reactive oxygen species (ROS) and ANG II. On the other hand, phospho-ERK1/2 expression increased on day 7 during the phase of enhanced mesangial cell (MC) proliferation and decreased thereafter. H(2)O(2) and ANG II each induced ERK5 phosphorylation by cultured rat MCs. Costimulation with both H(2)O(2) and ANG II synergistically increased ERK5 phosphorylation in MCs. Cultured MCs transfected with ERK5-specific small interference RNA showed a significant decrease in H(2)O(2) or ANG II-induced cell viability and soluble collagen secretion compared with control cells. Treatment of GN rats with an ANG II type 1 receptor blocker resulted in significant decreases in phospho-ERK5 expression and collagen accumulation accompanied by remarkable histological improvement. Taken together, these results suggest that MC ERK5 phosphorylation by ANG II or H(2)O(2) enhances cell viability and ECM accumulation in an experimental model of chronic GN.

Authors+Show Affiliations

Department of Pediatrics, Institute of Health Bioscience, University of Tokushima Graduate School, Tokushima, Japan. murushih@tulane.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19846573

Citation

Urushihara, Maki, et al. "ERK5 Activation Enhances Mesangial Cell Viability and Collagen Matrix Accumulation in Rat Progressive Glomerulonephritis." American Journal of Physiology. Renal Physiology, vol. 298, no. 1, 2010, pp. F167-76.
Urushihara M, Takamatsu M, Shimizu M, et al. ERK5 activation enhances mesangial cell viability and collagen matrix accumulation in rat progressive glomerulonephritis. Am J Physiol Renal Physiol. 2010;298(1):F167-76.
Urushihara, M., Takamatsu, M., Shimizu, M., Kondo, S., Kinoshita, Y., Suga, K., Kitamura, A., Matsuura, S., Yoshizumi, M., Tamaki, T., Kawachi, H., & Kagami, S. (2010). ERK5 activation enhances mesangial cell viability and collagen matrix accumulation in rat progressive glomerulonephritis. American Journal of Physiology. Renal Physiology, 298(1), F167-76. https://doi.org/10.1152/ajprenal.00124.2009
Urushihara M, et al. ERK5 Activation Enhances Mesangial Cell Viability and Collagen Matrix Accumulation in Rat Progressive Glomerulonephritis. Am J Physiol Renal Physiol. 2010;298(1):F167-76. PubMed PMID: 19846573.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ERK5 activation enhances mesangial cell viability and collagen matrix accumulation in rat progressive glomerulonephritis. AU - Urushihara,Maki, AU - Takamatsu,Masanori, AU - Shimizu,Maki, AU - Kondo,Shuji, AU - Kinoshita,Yukiko, AU - Suga,Kenichi, AU - Kitamura,Akiko, AU - Matsuura,Sato, AU - Yoshizumi,Masanori, AU - Tamaki,Toshiaki, AU - Kawachi,Hiroshi, AU - Kagami,Shoji, Y1 - 2009/10/21/ PY - 2009/10/23/entrez PY - 2009/10/23/pubmed PY - 2010/1/12/medline SP - F167 EP - 76 JF - American journal of physiology. Renal physiology JO - Am J Physiol Renal Physiol VL - 298 IS - 1 N2 - The mitogen-activated protein kinase (MAPK) cascade plays an important role in the regulation of various cellular functions in glomerulonephritis (GN). Here, we investigated whether extracellular signal-regulated kinase 5 (ERK5), a member of the MAPK family, is involved in the pathogenesis of chronic mesangioproliferative GN, using a rat model induced by uninephrectomy and anti-Thy-1 antibody injection. Immunostaining of kidneys obtained at different time points revealed that phospho-ERK5 was weakly expressed in control glomeruli but dramatically increased in a typical mesangial pattern after 28 and 56 days of GN. A semiquantitative assessment indicated that glomerular phospho-ERK5 expression closely paralleled the accumulation of extracellular matrix (ECM), collagen type I, as well as glomerular expression of reactive oxygen species (ROS) and ANG II. On the other hand, phospho-ERK1/2 expression increased on day 7 during the phase of enhanced mesangial cell (MC) proliferation and decreased thereafter. H(2)O(2) and ANG II each induced ERK5 phosphorylation by cultured rat MCs. Costimulation with both H(2)O(2) and ANG II synergistically increased ERK5 phosphorylation in MCs. Cultured MCs transfected with ERK5-specific small interference RNA showed a significant decrease in H(2)O(2) or ANG II-induced cell viability and soluble collagen secretion compared with control cells. Treatment of GN rats with an ANG II type 1 receptor blocker resulted in significant decreases in phospho-ERK5 expression and collagen accumulation accompanied by remarkable histological improvement. Taken together, these results suggest that MC ERK5 phosphorylation by ANG II or H(2)O(2) enhances cell viability and ECM accumulation in an experimental model of chronic GN. SN - 1522-1466 UR - https://www.unboundmedicine.com/medline/citation/19846573/ERK5_activation_enhances_mesangial_cell_viability_and_collagen_matrix_accumulation_in_rat_progressive_glomerulonephritis_ L2 - https://journals.physiology.org/doi/10.1152/ajprenal.00124.2009?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -