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CD74 in Kidney Disease.

Valiño-Rivas L, Baeza-Bermejillo C, Gonzalez-Lafuente L, Sanz AB, Ortiz A, Sanchez-Niño MD - Front Immunol (2015)

Bottom Line: However, CD74 may protect from interstitial kidney fibrosis.Furthermore, CD74 expression by stressed kidney cells raises questions about the kidney safety of cancer therapy strategies delivering lethal immunoconjugates to CD74-expressing cells.Thus, understanding CD74 biology in kidney cells is relevant for kidney therapeutics.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Universidad Autónoma de Madrid , Madrid , Spain.

ABSTRACT
CD74 (invariant MHC class II) regulates protein trafficking and is a receptor for macrophage migration inhibitory factor (MIF) and d-dopachrome tautomerase (d-DT/MIF-2). CD74 expression is increased in tubular cells and/or glomerular podocytes and parietal cells in human metabolic nephropathies, polycystic kidney disease, graft rejection and kidney cancer and in experimental diabetic nephropathy and glomerulonephritis. Stressors like abnormal metabolite (glucose, lyso-Gb3) levels and inflammatory cytokines increase kidney cell CD74. MIF activates CD74 to increase inflammatory cytokines in podocytes and tubular cells and proliferation in glomerular parietal epithelial cells and cyst cells. MIF overexpression promotes while MIF targeting protects from experimental glomerular injury and kidney cysts, and interference with MIF/CD74 signaling or CD74 deficiency protected from crescentic glomerulonephritis. However, CD74 may protect from interstitial kidney fibrosis. Furthermore, CD74 expression by stressed kidney cells raises questions about the kidney safety of cancer therapy strategies delivering lethal immunoconjugates to CD74-expressing cells. Thus, understanding CD74 biology in kidney cells is relevant for kidney therapeutics.

No MeSH data available.


Related in: MedlinePlus

CD74 functions in renal cells. Glomerular parietal epithelial cells express CD44 when activated and it is thought that CD44 contributes to the proliferative response. CD44 is not expressed by podocytes and its role of CD74 signaling in tubular cells has not been characterized. Thus, in tubular cells, CD44 is not depicted as part of the CD74 signaling complex. Cells expressing CXCR2, CXCR4, and CXCR7 are also indicated, although these receptors are depicted away from MIF when in that specific cell type, there is no information on their involvement in MIF signaling. In tubular epithelium with genetic defects in PKD1, MIF promotes tubular cell proliferation and cystogenesis and a CD74 antibody blocked the MIF-induced phosphorylation of ERK but not inflammatory responses.
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Figure 1: CD74 functions in renal cells. Glomerular parietal epithelial cells express CD44 when activated and it is thought that CD44 contributes to the proliferative response. CD44 is not expressed by podocytes and its role of CD74 signaling in tubular cells has not been characterized. Thus, in tubular cells, CD44 is not depicted as part of the CD74 signaling complex. Cells expressing CXCR2, CXCR4, and CXCR7 are also indicated, although these receptors are depicted away from MIF when in that specific cell type, there is no information on their involvement in MIF signaling. In tubular epithelium with genetic defects in PKD1, MIF promotes tubular cell proliferation and cystogenesis and a CD74 antibody blocked the MIF-induced phosphorylation of ERK but not inflammatory responses.

Mentions: Among kidney cells, MIF induced proliferation in parietal epithelial cells but not in podocytes (4) (Figure 1). Absence of CD44 or the terminal differentiation state of podocytes may account for the differences. MIF, MIF-2, CD74, and CD44 promote clear cell renal cell carcinoma, cell proliferation, and HIF-activation (38, 39). While MIF and MIF-2 overlap in controlling cell survival and tumor formation, MIF-2 plays a dominant role in renal cancer tumor growth in vivo (40). MIF also confers resistance to senescence and cell death in mesenchymal stem cells through CD74-dependent AMPK-FOXO3a signaling and c-Met activation (41).


CD74 in Kidney Disease.

Valiño-Rivas L, Baeza-Bermejillo C, Gonzalez-Lafuente L, Sanz AB, Ortiz A, Sanchez-Niño MD - Front Immunol (2015)

CD74 functions in renal cells. Glomerular parietal epithelial cells express CD44 when activated and it is thought that CD44 contributes to the proliferative response. CD44 is not expressed by podocytes and its role of CD74 signaling in tubular cells has not been characterized. Thus, in tubular cells, CD44 is not depicted as part of the CD74 signaling complex. Cells expressing CXCR2, CXCR4, and CXCR7 are also indicated, although these receptors are depicted away from MIF when in that specific cell type, there is no information on their involvement in MIF signaling. In tubular epithelium with genetic defects in PKD1, MIF promotes tubular cell proliferation and cystogenesis and a CD74 antibody blocked the MIF-induced phosphorylation of ERK but not inflammatory responses.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4585214&req=5

Figure 1: CD74 functions in renal cells. Glomerular parietal epithelial cells express CD44 when activated and it is thought that CD44 contributes to the proliferative response. CD44 is not expressed by podocytes and its role of CD74 signaling in tubular cells has not been characterized. Thus, in tubular cells, CD44 is not depicted as part of the CD74 signaling complex. Cells expressing CXCR2, CXCR4, and CXCR7 are also indicated, although these receptors are depicted away from MIF when in that specific cell type, there is no information on their involvement in MIF signaling. In tubular epithelium with genetic defects in PKD1, MIF promotes tubular cell proliferation and cystogenesis and a CD74 antibody blocked the MIF-induced phosphorylation of ERK but not inflammatory responses.
Mentions: Among kidney cells, MIF induced proliferation in parietal epithelial cells but not in podocytes (4) (Figure 1). Absence of CD44 or the terminal differentiation state of podocytes may account for the differences. MIF, MIF-2, CD74, and CD44 promote clear cell renal cell carcinoma, cell proliferation, and HIF-activation (38, 39). While MIF and MIF-2 overlap in controlling cell survival and tumor formation, MIF-2 plays a dominant role in renal cancer tumor growth in vivo (40). MIF also confers resistance to senescence and cell death in mesenchymal stem cells through CD74-dependent AMPK-FOXO3a signaling and c-Met activation (41).

Bottom Line: However, CD74 may protect from interstitial kidney fibrosis.Furthermore, CD74 expression by stressed kidney cells raises questions about the kidney safety of cancer therapy strategies delivering lethal immunoconjugates to CD74-expressing cells.Thus, understanding CD74 biology in kidney cells is relevant for kidney therapeutics.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Universidad Autónoma de Madrid , Madrid , Spain.

ABSTRACT
CD74 (invariant MHC class II) regulates protein trafficking and is a receptor for macrophage migration inhibitory factor (MIF) and d-dopachrome tautomerase (d-DT/MIF-2). CD74 expression is increased in tubular cells and/or glomerular podocytes and parietal cells in human metabolic nephropathies, polycystic kidney disease, graft rejection and kidney cancer and in experimental diabetic nephropathy and glomerulonephritis. Stressors like abnormal metabolite (glucose, lyso-Gb3) levels and inflammatory cytokines increase kidney cell CD74. MIF activates CD74 to increase inflammatory cytokines in podocytes and tubular cells and proliferation in glomerular parietal epithelial cells and cyst cells. MIF overexpression promotes while MIF targeting protects from experimental glomerular injury and kidney cysts, and interference with MIF/CD74 signaling or CD74 deficiency protected from crescentic glomerulonephritis. However, CD74 may protect from interstitial kidney fibrosis. Furthermore, CD74 expression by stressed kidney cells raises questions about the kidney safety of cancer therapy strategies delivering lethal immunoconjugates to CD74-expressing cells. Thus, understanding CD74 biology in kidney cells is relevant for kidney therapeutics.

No MeSH data available.


Related in: MedlinePlus