Hormonal modulation of glomerular function

1983 ◽  
Vol 244 (2) ◽  
pp. F95-F104 ◽  
Author(s):  
L. D. Dworkin ◽  
I. Ichikawa ◽  
B. M. Brenner
Keyword(s):  
Plasma Flow ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Renal Plasma Flow ◽  
Hydraulic Pressure ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
Glomerular Function ◽  
Hormonal Modulation

Glomeruli contain receptors for many hormones. Binding of angiotensin II (ANG II) or antidiuretic hormone (ADH) to glomerular mesangial cells elicits a contractile response. Other hormones induce synthesis of cyclic nucleotides (cAMP, cGMP). Glomeruli also synthesize several prostaglandins, renin, and ANG II. Micropuncture studies in Munich-Wistar rats have examined the effects of vasoactive drugs and hormones on the filtration process. Several vasodilators increase renal plasma flow in the dog and rat, but GFR remains relatively unchanged due to an offsetting fall in the ultrafiltration coefficient (Kf). Vasoconstrictor substances such as ANG II and norepinephrine cause declines in renal plasma flow and Kf, but GFR remains constant due to an increase in the transcapillary hydraulic pressure gradient. Antidiuretic peptides and parathyroid hormone also reduce Kf. Glomerular mesangial cells may regulate Kf by contracting and reducing glomerular capillary surface area. ANG II and ADH directly stimulate mesangial cell contraction in vitro. Other hormones appear to cause contraction by inducing local ANG II synthesis. These hormonal pathways are implicated in the pathogenesis of altered glomerular function in diverse forms of renal injury.

A mechanism by which atrial natriuretic factor mediates its glomerular actions

1986 ◽  
Vol 251 (6) ◽  
pp. F1036-F1042 ◽  
Author(s):  
R. G. Appel ◽  
J. Wang ◽  
M. S. Simonson ◽  
M. J. Dunn
Keyword(s):  
Mesangial Cell ◽  
Mesangial Cells ◽  
Dependent Manner ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
Sprague Dawley ◽  
Cell Contraction ◽  
Concentration Dependent Manner ◽  
Cell Contractility

Differential in vivo glomerular effects of atriopeptin I (AP I) and atriopeptin III (AP III) were studied in parallel with in vitro physiological and biochemical parameters. In anesthetized Sprague-Dawley rats, AP III, but not AP I, significantly increased glomerular filtration rate. Image analysis microscopy was used to assess the effect of AP I and AP III on angiotensin II (ANG II)-induced contraction of cultured rat glomerular mesangial cells. AP III, but not AP I, inhibited ANG II-induced mesangial cell contraction in a concentration-dependent manner. Additional inhibitory agents included exogenous DBcGMP, 8-BrcGMP, Na nitroprusside, and DBcAMP. AP III stimulated mesangial cell cGMP with a lower threshold and greater maximum stimulation than AP I. Neither agent stimulated cAMP accumulation. Since mesangial cell contractility may regulate the glomerular capillary surface area, these results suggest that AP III partially mediates its glomerular effects through inhibition of ANG II-induced mesangial cell contraction. Whereas cGMP is not clearly implicated as the mediator of this effect, it appears that both cGMP and cAMP may regulate the state of mesangial cell contractility.

scholarly journals Mesangial cell proteoglycans: synthesis and metabolism.

1992 ◽  
Vol 2 (10) ◽  
pp. S88
Author(s):  
M Davies ◽  
G J Thomas ◽  
L D Shewring ◽  
R M Mason
Keyword(s):  
Culture Medium ◽  
Mesangial Cell ◽  
Dermatan Sulfate ◽  
Mesangial Cells ◽  
Core Protein ◽  
Glomerular Mesangial Cells ◽  
Cellular Processes ◽  
Specialized Function ◽  
In Cells

In cultures of human adult glomerular mesangial cells, large chondroitin sulfate proteoglycans (CSPG) and small dermatan sulfate proteoglycans (DSPG) are synthesized. The large CSPG has a core protein, M(r) of 400,000 (major) and M(r) of 500,000 (minor), and binds to hyaluronic acid to form large aggregates. The two small DSPGs (Mr of approximately 350,000 and M(r) of approximately 200,000) were related to biglycan and decorin, respectively. The majority of these proteoglycans were located in the culture medium, but a hydrophobic form of the CSPG was extracted from the cell layer. Mesangial cells in the growing phase synthesized and secreted all three types of proteoglycans, but in cells arrested in G0 by serum deprivation the incorporation of (35S)sulfate in CSPG was drastically reduced. In the same cells stimulated to proliferate by replacing the medium with one containing serum, the synthesis of CSPG dramatically enhanced. The synthesis of CSPG and DSPG was also elevated in cells cocultured with cytokines but in contrast was significantly reduced when cultured in medium containing hyperglycemic levels of glucose. Finally, preliminary experiments are reported that indicate that CSPG and DSPG bind to low-density lipoproteins in vitro. These observations suggest a possible specialized function for proteoglycans in cellular processes characteristic of glomerular disease.

scholarly journals Endothelium-derived relaxing factor, nitric oxide: effects on and production by mesangial cells and the glomerulus.

1993 ◽  
Vol 3 (8) ◽  
pp. 1435-1441
Author(s):  
L Raij ◽  
P J Shultz
Keyword(s):  
Nitric Oxide ◽  
Vascular Tone ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Glomerular Mesangial Cells ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor

The endothelium-derived relaxing factor nitric oxide (EDRF/NO) is a labile, endogenous vasodilator that is important in the control of systemic vascular tone. This review focuses on the effects of EDRF/NO on glomerular mesangial cells in vitro and on the role of EDRF/NO in mesangial and glomerular physiology and pathophysiology in vivo. It was concluded that EDRF/NO can stimulate increases in cGMP, inhibit mesangial cell contraction, and inhibit growth factor-induced proliferation of mesangial cells in culture. Furthermore, incubation with endotoxin or cytokines stimulates mesangial cells to produce EDRF/NO, via an inducible NO synthase enzyme. Therefore, it is likely that NO could play a role in the inflammatory response within the glomerulus. Finally, recent studies providing evidence that EDRF/NO is functional within the glomerulus in vivo, especially during endotoxemia and inflammation are also reviewed.

Effect of angiotensin II on Ca2+ kinetics and contraction in cultured rat glomerular mesangial cells

1988 ◽  
Vol 254 (2) ◽  
pp. F254-F266 ◽  
Author(s):  
K. Takeda ◽  
H. Meyer-Lehnert ◽  
J. K. Kim ◽  
R. W. Schrier
Keyword(s):  
Angiotensin Ii ◽  
Cell Shape ◽  
Mesangial Cells ◽  
In Vitro Study ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
Glomerular Mesangial Cell ◽  
High Potassium ◽  
Voltage Dependent

This in vitro study was undertaken to determine the changes in Ca2+ kinetics and cell shape of cultured putative glomerular mesangial cells in the rat in response to angiotensin II (ANG II). Intracellular Ca2+ ([Ca2+]i) was measured using quin 2. ANG II-stimulated Ca2+ efflux was also determined. ANG II induced rapid concentration-dependent increases in [Ca2+]i and Ca2+ efflux. ANG II also induced contraction of mesangial cells as assessed by alterations in cell shape. Even in Ca2+-free medium, ANG II increased [Ca2+]i and Ca2+ efflux, but to a lesser extent. Under this condition, contraction of mesangial cells induced by ANG II was also observed. Readdition of extracellular Ca2+ after the ANG II-induced increase in [Ca2+]i caused a second and slower [Ca2+]i increase. High potassium (50 mM) induced a change of [Ca2+]i, but to a lesser extent compared with the ANG II-induced change. The Ca2+ channel blocker verapamil (5 x 10(-5) M) partially inhibited ANG II-induced Ca2+ influx but totally blocked the increase in [Ca2+]i induced by high potassium. Verapamil did not inhibit ANG II-stimulated Ca2+ efflux or the change in cell shape. Dantrolene (10(-4) M), a blocker of Ca2+ release from endoplasmic reticulum, inhibited ANG II-stimulated Ca2+ efflux and change in cell shape. These results indicate that ANG II rapidly increases [Ca2+]i in cultured rat mesangial cells, in part by mobilizing Ca2+ from dantrolene-sensitive intracellular pools and in part through activation of receptor-operated and voltage-dependent Ca2+ channels. The [Ca2+]i mobilization, however, seems to be the primary modulator of initial glomerular mesangial cell contraction.

Extracellular glucose reduces the responsiveness of mesangial cell ion channels to angiotensin II

1995 ◽  
Vol 269 (3) ◽  
pp. F389-F397 ◽  
Author(s):  
E. E. Seal ◽  
D. C. Eaton ◽  
L. M. Gomez ◽  
H. Ma ◽  
B. N. Ling
Keyword(s):  
Angiotensin Ii ◽  
Ion Channels ◽  
High Glucose ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Ion Homeostasis ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
Extracellular Glucose ◽  
Normal Glucose

Abnormal cellular ion homeostasis is a well-recognized component of diabetic glomerular disease. In cultured rat glomerular mesangial cells, we have previously shown that insulin regulates Ca(2+)-dependent activation of 4-pS Cl- channels and 27-pS nonselective cation channels (NSCC) by angiotensin II (ANG II). To assess whether extracellular glucose also affects mesangial ion channels, we applied patch-clamp techniques to cells incubated in constant insulin (100 mU/ml) and either "normal" (5 mM) or "high" (30 mM) glucose for 1 wk. In normal glucose, 100 nM ANG II increased Cl- and NSCC activity by > 16-fold and > 60-fold, respectivley. Direct release of intracellular Ca2+ ([Ca2+]i) stores (0.25 microM thapsigargin) mimicked ANG II-induced channel stimulation. In high glucose, Cl- and NSCC stimulation by ANG II was attenuated (< 7-fold), whereas channel activation by thapsigargin was unaffected. Protein kinase C (PKC) inhibition (30-min exposure to 0.5 microM calphostin) or downregulation (24-h exposure to 0.1 microM 4 beta-phorbol 12-myristate 13-acetate), but not aldose reductase inhibition (0.5 mM sorbinil), restored channel responsiveness to ANG II despite high glucose. Channel responsiveness was also restored if mesangial cells were coincubated in both high glucose and 500 microM myo-inositol. Acute exposure to a synthetic diacylglycerol (100 microM 1-oleoyl-2-acetyl glycerol) reestablished channel unresponsiveness to ANG II. We conclude the following in rat mesangial cell cultures: 1) Activation of Ca(2+)-dependent Cl- and NSCCs by ANG II is reduced by high extracellular glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of leukotrienes on isolated rat glomeruli and cultured mesangial cells

1986 ◽  
Vol 250 (5) ◽  
pp. F838-F844
Author(s):  
R. Barnett ◽  
P. Goldwasser ◽  
L. A. Scharschmidt ◽  
D. Schlondorff
Keyword(s):  
Surface Area ◽  
Mesangial Cells ◽  
Shape Change ◽  
Ang Ii ◽  
Planar Surface ◽  
Glomerular Function ◽  
Shape Changes ◽  
Isolated Rat

Several vasoactive substances influence glomerular function in vivo and alter glomerular surface area and prostaglandin (PG) synthesis in vitro. Leukotrienes (LT) LTC4 and LTD4 may also influence glomerular function in vivo and in the isolated perfused kidney. We therefore compared the effects of LT with those of angiotensin II (ANG II), arginine vasopressin (AVP), and platelet activating factor (PAF) on planar surface area of isolated rat glomeruli and the shape change of cultured mesangial cells and their PG synthesis. ANG II, AVP, and PAF decreased the surface area of isolated rat glomeruli by 10-14% with comparable changes induced by LTC4 and LTD4. Half-maximal effects of LTs were observed at approximately 10(-7) M. Incubation of cultured rat mesangial cells with LTC4 or LTD4 at 10(-7) and 10(-8) M was also associated with shape changes of the cells resulting in significant reductions in planar surface area in a dose- and time-dependent fashion similar to that noted previously with other vasoactive agents. In cells grown on a flexible silicone rubber support, LTD4 resulted in rapid increases in wrinkling of the mobile surface indicating that the shape change may represent cell contraction. The LT-mediated decrease in surface area of glomeruli and mesangial cells was partially antagonized by the LT inhibitor FPL-55712. In contrast to the 11- and 7-fold enhancement of PGE2 synthesis in cultured mesangial cells by ANG II or PAF, neither LTC4 nor LTD4 affected PGE2 production. These results demonstrate that LTC4 and LTD4 cause mesangial shape changes that in the whole glomerulus may decrease glomerular surface area.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetic rat glomerular mesangial cells display normal inositol trisphosphate and calcium release

1992 ◽  
Vol 263 (4) ◽  
pp. F649-F655 ◽  
Author(s):  
R. D. Hurst ◽  
C. I. Whiteside ◽  
J. C. Thompson
Keyword(s):  
Calcium Release ◽  
Mesangial Cells ◽  
Inositol Phosphates ◽  
Inositol Trisphosphate ◽  
Diabetic Rat ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
Isolated Glomeruli ◽  
Planar Area

Since diabetes may cause cellular myo-inositol depletion, we investigated whether the observed in vitro hypocontractile response of streptozotocin (STZ)-treated rat glomeruli to angiotensin II (ANG II) is associated with an alteration in inositol trisphosphate (IP3) mobilization of intracellular Ca2+. Contraction of diabetic isolated glomeruli induced by ANG II (5 microM), measured in vitro by changes in the planar area, was reduced by 60%, compared with normal up to 60 min (P < 0.05). In cells of isolated glomeruli, preloaded with myo-[3H]inositol, production of [3H]inositol phosphates ([3H]IPs) and [3H]inositol trisphosphate ([3H]IP3) was analyzed by Dowex chromatography. ANG II (1 microM) evoked an immediate peak (5-10 s) in total [3H]IPs of 60.5 +/- 18.8% (mean +/- SE) above basal (nonstimulated state) in normal glomeruli, and 88.4 +/- 19.4% in diabetic condition [not significant (NS), n = 8]. At 60 s, the normal and diabetic total [3H]IPs responses were not significantly different from each other. The immediate (10 s) [3H]IP3 response from normal glomeruli, 8.1 +/- 7.9% above basal, was not significantly different from that of diabetic glomeruli, 15.7 +/- 7.4%. ANG II receptor-mediated rise in cytosolic Ca2+ in the cells of normal and diabetic isolated glomeruli was compared by measuring the efflux of 45Ca2+. Isolated glomeruli were preloaded with 45Ca2+. Following ANG II stimulation, peak 45Ca2+ efflux values at 1 min were 141.7 +/- 15.9% (normal) vs. 143.7 +/- 7.8% (diabetic) of baseline (100%), respectively (NS, n = 4). Thapsigargin, 2 microM, specifically prevented ANG II-stimulated and IP3-mediated 45Ca2+ efflux (73% inhibition, P < 0.001) from cells of whole glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS)

Mesangial cell-derived factors alter monocyte activation and function through inflammatory pathways: possible pathogenic role in diabetic nephropathy

2009 ◽  
Vol 297 (5) ◽  
pp. F1229-F1237 ◽  
Author(s):  
Danqing Min ◽  
J. Guy Lyons ◽  
James Bonner ◽  
Stephen M. Twigg ◽  
Dennis K. Yue ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Conditioned Medium ◽  
High Glucose ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Glomerular Mesangial Cells ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tnf Α ◽  
Cell Conditioned Medium

Infiltration of macrophages to the kidney is a feature of early diabetic nephropathy. For this to happen monocytes must become activated, migrate from the circulation, and infiltrate the mesangium. This process involves degradation of extracellular matrix, a process mediated by matrix metalloproteinases (MMPs). In the present study we investigate the expression of proinflammatory cytokines TNF-α, IL-6, and MMP-9 in glomeruli of control and diabetic rodents and use an in vitro coculture system to examine whether factors secreted by mesangial cells in response to a diabetic milieu can induce monocyte MMP-9 expression and infiltration. After 8 wk of diabetes, the glomerular level of TNF-α, IL-6, and macrophage number and colocalization of MMP-9 with macrophage were increased ( P < 0.01). Coculture of THP1 monocytes and glomerular mesangial cells in 5 or 25 mM glucose increased MMP-9 (5 mM: 65% and 25 mM: 112%; P < 0.05) and conditioned media degradative activity (5 mM: 30.0% and 25 mM: 33.5%: P < 0.05). These effects were reproduced by addition of mesangial cell conditioned medium to THP1 cells. High glucose (25 mM) increased TNF-α, IL-6, and monocyte chemoattractant protein-1 in mesangial cell conditioned medium. These cytokines all increased adhesion and differentiation of THP1 cells ( P < 0.05), but only TNF-α and IL-6 increased MMP-9 expression (50- and 60-fold, respectively; P < 0.05). Our results show that mesangial cell-secreted factors increase monocyte adhesion, differentiation, MMP expression, and degradative capacity. High glucose could augment these effects by increasing mesangial cell proinflammatory cytokine secretion. This mesangial cell-monocyte interaction may be important in activating monocytes to migrate from the circulation to the kidney in the early stages of diabetic nephropathy.

scholarly journals Glomerular mesangial cell recruitment and function require the co-receptor neuropilin-1

2017 ◽  
Vol 313 (6) ◽  
pp. F1232-F1242 ◽  
Author(s):  
Christina S. Bartlett ◽  
Rizaldy P. Scott ◽  
Isabel Anna Carota ◽  
Monika L. Wnuk ◽  
Yashpal S. Kanwar ◽  
...  
Keyword(s):  
Mesangial Cell ◽  
Mesangial Cells ◽  
Cell Types ◽  
Glomerular Mesangial Cell ◽  
Glomerular Function ◽  
Cell Recruitment ◽  
Neuropilin 1 ◽  
Biochemical Analyses ◽  
And Function

Proteinuria has been reported in cancer patients receiving agents that target the transmembrane receptor neuropilin-1 (Nrp1) suggesting potential adverse effects on glomerular function. Here we show that Nrp1 is highly expressed by mesangial cells and that genetic deletion of the Nrp1 gene from PDGF receptor-β+ mesangial cells results in proteinuric disease and glomerulosclerosis, leading to renal failure and death within 6 wk of age in mice. The major defect is a failure of mesangial cell migration that is required to establish the mature glomerular tuft. In vitro data show that the potent chemotactic effect of PDGFB is lost in Nrp1-deficient mesangial cells. Biochemical analyses reveal that Nrp1 is required for PDGFB-dependent phosphorylation of p130 Crk-associated substrate (p130Cas), a large-scaffold molecule that is involved in motility of other cell types. In stark contrast, matrix adhesion and activation of ERK and Akt, which mediate proliferation of mesangial cells in response to PDGFB, are unaffected by the absence of Nrp1. Taken together, these results identify a critical cell-autonomous role for Nrp1 in the migratory behavior of mesangial cells and may help explain the renal effects that occur in patients receiving Nrp1-inhibitory drugs.

scholarly journals Glomerular mesangial cells in vitro synthesize an aggregating proteoglycan immunologically related to versican

1994 ◽  
Vol 302 (1) ◽  
pp. 49-56 ◽  
Author(s):  
G J Thomas ◽  
M T Bayliss ◽  
K Harper ◽  
R M Mason ◽  
M Davies
Keyword(s):  
Mesangial Cell ◽  
Mesangial Cells ◽  
Core Protein ◽  
Chondroitin Sulphate ◽  
Heparan Sulphate ◽  
Gel Chromatography ◽  
Glomerular Mesangial Cells ◽  
Glomerular Cell ◽  
Core Proteins

Recent studies have shown that mesangial cells derived from human adult glomeruli synthesize a number of 35S-labelled proteoglycans including a large chondroitin sulphate proteoglycan (CSPG), two dermatan sulphate proteoglycans (biglycan and decorin) and two heparan sulphate proteoglycans [Thomas, Mason and Davies (1991) Biochem. J. 277, 81-88]. In the present study we have examined the interaction of these proteoglycans with hyaluronan (HA) using associative gel chromatography. Only the large CSPG bound to HA, with 60% of those molecules in the medium and 80% of those in the cell layer being able to interact. Reduction and alkylation, or treatment of the monomer CSPG with proteinases, prevented the formation of aggregates, suggesting that the core protein was involved. The aggregates formed between purified CSPG and HA could be dissociated in the presence of HA-oligosaccharides of at least 10 monosaccharides in length. The inclusion of link protein with CSPG and HA promoted the formation of aggregates. Experiments with 3H-labelled mesangial-cell proteoglycans confirmed that only the large CSPG, with core protein molecular masses of 400 kDa and 500 kDa, interacted with HA. After chondroitin ABC lyase treatment of CSPG isolated from conditioned culture medium, several bands similar to those observed with 3H-labelled core proteins were identified using a polyclonal antiserum that recognizes versican. A monoclonal antibody recognizing the 1-C-6 epitope in the G1 and G2 globular regions of aggrecan did not recognize either mesangial-cell CSPG or bovine aortic versican. Northern-blot analysis confirmed that human mesangial cells express versican. Thus human mesangial large CSPG is a member of the versican family of proteoglycans. The interaction of CSPG and HA within the glomerulus may be important in glomerular cell migration and proliferation.

Sign in / Sign up

Export Citation Format

Share Document