Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1996 Dec;149(6):2037–2054.

Human mast cell basic fibroblast growth factor in pulmonary fibrotic disorders.

Y Inoue 1, T E King Jr 1, S S Tinkle 1, K Dockstader 1, L S Newman 1
PMCID: PMC1865345  PMID: 8952537

Abstract

Mast cells (MCs) are abundant in fibrotic tissue, although their role in fibrogenesis remains obscure. Recent studies suggest MCs may produce basic fibroblast growth factor (bFGF). To evaluate the hypothesis that MC bFGF contributes to the fibrotic response in human interstitial lung disease, we studied lung tissue, bronchoalveolar lavage fluid and serum in 1) idiopathic pulmonary fibrosis, 2) chronic beryllium disease and sarcoidosis, 3) control subjects with no disease or who were beryllium sensitized with normal lung histology. Diseased subjects underwent clinical assessments to stage disease severity. We determined that most bFGF+ cells in lung interstitium are MCs and are most abundant in idiopathic pulmonary fibrosis. Distribution of bFGF+ MCs matched that of extracellular matrix deposition and correlated with the extent of fibrosis morphometrically. Only one bFGF isoform (17.8 kd) was found in idiopathic pulmonary fibrosis and chronic beryllium disease lung tissues and interacted with heparin-like molecules in the lung. Using a human MC line, we verified that MCs express bFGF mRNA and protein that localizes to cytoplasmic granules. Clinically, bFGF concentrations in bronchoalveolar lavage fluid and serum were highest in disease states and correlated with bronchoalveolar lavage cellularity and severity of gas exchange abnormalities, supporting a role for MC bFGF in the pulmonary fibrotic response and its clinical consequence.

Full text

PDF
2037

Images in this article

2042Figure 1
on p.2042
2043Figure 2
on p.2043
2045Figure 7
on p.2045
2046Figure 10
on p.2046
2047Figure 11
on p.2047
2047Figure 12
on p.2047

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BLAKEMORE W. S., FORSTER R. E., MORTON J. W., OGILVIE C. M. A standardized breath holding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide. J Clin Invest. 1957 Jan;36(1 Pt 1):1–17. doi: 10.1172/JCI103402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bashkin P., Doctrow S., Klagsbrun M., Svahn C. M., Folkman J., Vlodavsky I. Basic fibroblast growth factor binds to subendothelial extracellular matrix and is released by heparitinase and heparin-like molecules. Biochemistry. 1989 Feb 21;28(4):1737–1743. doi: 10.1021/bi00430a047. [DOI] [PubMed] [Google Scholar]
  3. Bjermer L., Engström-Laurent A., Thunell M., Hällgren R. The mast cell and signs of pulmonary fibroblast activation in sarcoidosis. Int Arch Allergy Appl Immunol. 1987;82(3-4):298–301. doi: 10.1159/000234212. [DOI] [PubMed] [Google Scholar]
  4. Blotnick S., Peoples G. E., Freeman M. R., Eberlein T. J., Klagsbrun M. T lymphocytes synthesize and export heparin-binding epidermal growth factor-like growth factor and basic fibroblast growth factor, mitogens for vascular cells and fibroblasts: differential production and release by CD4+ and CD8+ T cells. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):2890–2894. doi: 10.1073/pnas.91.8.2890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bost T. W., Riches D. W., Schumacher B., Carré P. C., Khan T. Z., Martinez J. A., Newman L. S. Alveolar macrophages from patients with beryllium disease and sarcoidosis express increased levels of mRNA for tumor necrosis factor-alpha and interleukin-6 but not interleukin-1 beta. Am J Respir Cell Mol Biol. 1994 May;10(5):506–513. doi: 10.1165/ajrcmb.10.5.8179912. [DOI] [PubMed] [Google Scholar]
  6. Bradding P., Roberts J. A., Britten K. M., Montefort S., Djukanovic R., Mueller R., Heusser C. H., Howarth P. H., Holgate S. T. Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines. Am J Respir Cell Mol Biol. 1994 May;10(5):471–480. doi: 10.1165/ajrcmb.10.5.8179909. [DOI] [PubMed] [Google Scholar]
  7. Buch S., Han R. N., Liu J., Moore A., Edelson J. D., Freeman B. A., Post M., Tanswell A. K. Basic fibroblast growth factor and growth factor receptor gene expression in 85% O2-exposed rat lung. Am J Physiol. 1995 Mar;268(3 Pt 1):L455–L464. doi: 10.1152/ajplung.1995.268.3.L455. [DOI] [PubMed] [Google Scholar]
  8. Bugler B., Amalric F., Prats H. Alternative initiation of translation determines cytoplasmic or nuclear localization of basic fibroblast growth factor. Mol Cell Biol. 1991 Jan;11(1):573–577. doi: 10.1128/mcb.11.1.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Burd P. R., Rogers H. W., Gordon J. R., Martin C. A., Jayaraman S., Wilson S. D., Dvorak A. M., Galli S. J., Dorf M. E. Interleukin 3-dependent and -independent mast cells stimulated with IgE and antigen express multiple cytokines. J Exp Med. 1989 Jul 1;170(1):245–257. doi: 10.1084/jem.170.1.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Butterfield J. H., Weiler D., Dewald G., Gleich G. J. Establishment of an immature mast cell line from a patient with mast cell leukemia. Leuk Res. 1988;12(4):345–355. doi: 10.1016/0145-2126(88)90050-1. [DOI] [PubMed] [Google Scholar]
  11. Charlotte F., Win K. M., Preaux A. M., Mavier P., Dhumeaux D., Zafrani E. S., Rosenbaum J. Immunolocalization of heparin-binding growth factors (HBGF) types 1 and 2 in rat liver. Selective hyperexpression of HBGF-2 in carbon tetrachloride-induced fibrosis. J Pathol. 1993 Apr;169(4):471–476. doi: 10.1002/path.1711690414. [DOI] [PubMed] [Google Scholar]
  12. Cherniack R. M., Colby T. V., Flint A., Thurlbeck W. M., Waldron J., Ackerson L., King T. E., Jr Quantitative assessment of lung pathology in idiopathic pulmonary fibrosis. The BAL Cooperative Group Steering Committee. Am Rev Respir Dis. 1991 Oct;144(4):892–900. doi: 10.1164/ajrccm/144.4.892. [DOI] [PubMed] [Google Scholar]
  13. Crapo R. O., Morris A. H. Standardized single breath normal values for carbon monoxide diffusing capacity. Am Rev Respir Dis. 1981 Feb;123(2):185–189. doi: 10.1164/arrd.1981.123.2.185. [DOI] [PubMed] [Google Scholar]
  14. Doherty D. E., Downey G. P., Schwab B., 3rd, Elson E., Worthen G. S. Lipolysaccharide-induced monocyte retention in the lung. Role of monocyte stiffness, actin assembly, and CD18-dependent adherence. J Immunol. 1994 Jul 1;153(1):241–255. [PubMed] [Google Scholar]
  15. Dvorak A. M. Ultrastructural analysis of human mast cells and basophils. Chem Immunol. 1995;61:1–33. [PubMed] [Google Scholar]
  16. Florkiewicz R. Z., Shibata F., Barankiewicz T., Baird A., Gonzalez A. M., Florkiewicz E., Shah N. Basic fibroblast growth factor gene expression. Ann N Y Acad Sci. 1991;638:109–126. doi: 10.1111/j.1749-6632.1991.tb49022.x. [DOI] [PubMed] [Google Scholar]
  17. Florkiewicz R. Z., Sommer A. Human basic fibroblast growth factor gene encodes four polypeptides: three initiate translation from non-AUG codons. Proc Natl Acad Sci U S A. 1989 Jun;86(11):3978–3981. doi: 10.1073/pnas.86.11.3978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Folkman J., Klagsbrun M., Sasse J., Wadzinski M., Ingber D., Vlodavsky I. A heparin-binding angiogenic protein--basic fibroblast growth factor--is stored within basement membrane. Am J Pathol. 1988 Feb;130(2):393–400. [PMC free article] [PubMed] [Google Scholar]
  19. Fu Y. M., Spirito P., Yu Z. X., Biro S., Sasse J., Lei J., Ferrans V. J., Epstein S. E., Casscells W. Acidic fibroblast growth factor in the developing rat embryo. J Cell Biol. 1991 Sep;114(6):1261–1273. doi: 10.1083/jcb.114.6.1261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. GOLDMAN H. I., BECKLAKE M. R. Respiratory function tests; normal values at median altitudes and the prediction of normal results. Am Rev Tuberc. 1959 Apr;79(4):457–467. doi: 10.1164/artpd.1959.79.4.457. [DOI] [PubMed] [Google Scholar]
  21. Gonzalez A. M., Buscaglia M., Fox R., Isacchi A., Sarmientos P., Farris J., Ong M., Martineau D., Lappi D. A., Baird A. Basic fibroblast growth factor in Dupuytren's contracture. Am J Pathol. 1992 Sep;141(3):661–671. [PMC free article] [PubMed] [Google Scholar]
  22. Gordon J. R., Galli S. J. Mast cells as a source of both preformed and immunologically inducible TNF-alpha/cachectin. Nature. 1990 Jul 19;346(6281):274–276. doi: 10.1038/346274a0. [DOI] [PubMed] [Google Scholar]
  23. Gordon J. R., Galli S. J. Promotion of mouse fibroblast collagen gene expression by mast cells stimulated via the Fc epsilon RI. Role for mast cell-derived transforming growth factor beta and tumor necrosis factor alpha. J Exp Med. 1994 Dec 1;180(6):2027–2037. doi: 10.1084/jem.180.6.2027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Gospodarowicz D., Ferrara N., Schweigerer L., Neufeld G. Structural characterization and biological functions of fibroblast growth factor. Endocr Rev. 1987 May;8(2):95–114. doi: 10.1210/edrv-8-2-95. [DOI] [PubMed] [Google Scholar]
  25. Gospodarowicz D. Fibroblast growth factor. Crit Rev Oncog. 1989;1(1):1–26. [PubMed] [Google Scholar]
  26. Hawkins R. A., Claman H. N., Clark R. A., Steigerwald J. C. Increased dermal mast cell populations in progressive systemic sclerosis: a link in chronic fibrosis? Ann Intern Med. 1985 Feb;102(2):182–186. doi: 10.7326/0003-4819-102-2-182. [DOI] [PubMed] [Google Scholar]
  27. Henke C., Fiegel V., Peterson M., Wick M., Knighton D., McCarthy J., Bitterman P. Identification and partial characterization of angiogenesis bioactivity in the lower respiratory tract after acute lung injury. J Clin Invest. 1991 Oct;88(4):1386–1395. doi: 10.1172/JCI115445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Henke C., Marineili W., Jessurun J., Fox J., Harms D., Peterson M., Chiang L., Doran P. Macrophage production of basic fibroblast growth factor in the fibroproliferative disorder of alveolar fibrosis after lung injury. Am J Pathol. 1993 Oct;143(4):1189–1199. [PMC free article] [PubMed] [Google Scholar]
  29. Henson P. M., Johnston R. B., Jr Tissue injury in inflammation. Oxidants, proteinases, and cationic proteins. J Clin Invest. 1987 Mar;79(3):669–674. doi: 10.1172/JCI112869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Hirose N., Lynch D. A., Cherniack R. M., Doherty D. E. Correlation between high resolution computed tomography and tissue morphometry of the lung in bleomycin-induced pulmonary fibrosis in the rabbit. Am Rev Respir Dis. 1993 Mar;147(3):730–738. doi: 10.1164/ajrccm/147.3.730. [DOI] [PubMed] [Google Scholar]
  31. Hunt L. W., Colby T. V., Weiler D. A., Sur S., Butterfield J. H. Immunofluorescent staining for mast cells in idiopathic pulmonary fibrosis: quantification and evidence for extracellular release of mast cell tryptase. Mayo Clin Proc. 1992 Oct;67(10):941–948. doi: 10.1016/s0025-6196(12)60924-0. [DOI] [PubMed] [Google Scholar]
  32. Hyde D. M., King T. E., Jr, McDermott T., Waldron J. A., Jr, Colby T. V., Thurlbeck W. M., Flint W. M., Ackerson L., Cherniack R. M. Idiopathic pulmonary fibrosis. Quantitative assessment of lung pathology. Comparison of a semiquantitative and a morphometric histopathologic scoring system. Am Rev Respir Dis. 1992 Oct;146(4):1042–1047. doi: 10.1164/ajrccm/146.4.1042. [DOI] [PubMed] [Google Scholar]
  33. Jordana M. Mast cells and fibrosis--who's on first? Am J Respir Cell Mol Biol. 1993 Jan;8(1):7–8. doi: 10.1165/ajrcmb/8.1.7. [DOI] [PubMed] [Google Scholar]
  34. Kawanami O., Ferrans V. J., Fulmer J. D., Crystal R. G. Ultrastructure of pulmonary mast cells in patients with fibrotic lung disorders. Lab Invest. 1979 Jun;40(6):717–734. [PubMed] [Google Scholar]
  35. Kennedy S. H., Qin H., Lin L., Tan E. M. Basic fibroblast growth factor regulates type I collagen and collagenase gene expression in human smooth muscle cells. Am J Pathol. 1995 Mar;146(3):764–771. [PMC free article] [PubMed] [Google Scholar]
  36. Kleeberger S. R., Seiden J. E., Levitt R. C., Zhang L. Y. Mast cells modulate acute ozone-induced inflammation of the murine lung. Am Rev Respir Dis. 1993 Nov;148(5):1284–1291. doi: 10.1164/ajrccm/148.5.1284. [DOI] [PubMed] [Google Scholar]
  37. Li Q. Y., Raza-Ahmad A., MacAulay M. A., Lalonde L. D., Rowden G., Trethewey E., Dean S. The relationship of mast cells and their secreted products to the volume of fibrosis in posttransplant hearts. Transplantation. 1992 May;53(5):1047–1051. doi: 10.1097/00007890-199205000-00015. [DOI] [PubMed] [Google Scholar]
  38. Lindner V., Reidy M. A. Proliferation of smooth muscle cells after vascular injury is inhibited by an antibody against basic fibroblast growth factor. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3739–3743. doi: 10.1073/pnas.88.9.3739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Lykke A. W., Schonell M. E., Stewart B. W. Atypical mast cell degranulation and focal hydropic degeneration of venular endothelium in diffuse fibrosing alveolitis. Experientia. 1979 Nov 15;35(11):1492–1493. doi: 10.1007/BF01962804. [DOI] [PubMed] [Google Scholar]
  40. MOVAT H. Z. Demonstration of all connective tissue elements in a single section; pentachrome stains. AMA Arch Pathol. 1955 Sep;60(3):289–295. [PubMed] [Google Scholar]
  41. Matsuzaki K., Yoshitake Y., Matuo Y., Sasaki H., Nishikawa K. Monoclonal antibodies against heparin-binding growth factor II/basic fibroblast growth factor that block its biological activity: invalidity of the antibodies for tumor angiogenesis. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9911–9915. doi: 10.1073/pnas.86.24.9911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Mignatti P., Morimoto T., Rifkin D. B. Basic fibroblast growth factor, a protein devoid of secretory signal sequence, is released by cells via a pathway independent of the endoplasmic reticulum-Golgi complex. J Cell Physiol. 1992 Apr;151(1):81–93. doi: 10.1002/jcp.1041510113. [DOI] [PubMed] [Google Scholar]
  43. Mori H., Kawada K., Zhang P., Uesugi Y., Sakamoto O., Koda A. Bleomycin-induced pulmonary fibrosis in genetically mast cell-deficient WBB6F1-W/Wv mice and mechanism of the suppressive effect of tranilast, an antiallergic drug inhibiting mediator release from mast cells, on fibrosis. Int Arch Allergy Appl Immunol. 1991;95(2-3):195–201. doi: 10.1159/000235429. [DOI] [PubMed] [Google Scholar]
  44. Newman L. S., Bobka C., Schumacher B., Daniloff E., Zhen B., Mroz M. M., King T. E., Jr Compartmentalized immune response reflects clinical severity of beryllium disease. Am J Respir Crit Care Med. 1994 Jul;150(1):135–142. doi: 10.1164/ajrccm.150.1.8025739. [DOI] [PubMed] [Google Scholar]
  45. Newman L. S., Kreiss K., King T. E., Jr, Seay S., Campbell P. A. Pathologic and immunologic alterations in early stages of beryllium disease. Re-examination of disease definition and natural history. Am Rev Respir Dis. 1989 Jun;139(6):1479–1486. doi: 10.1164/ajrccm/139.6.1479. [DOI] [PubMed] [Google Scholar]
  46. Nilsson G., Blom T., Kusche-Gullberg M., Kjellén L., Butterfield J. H., Sundström C., Nilsson K., Hellman L. Phenotypic characterization of the human mast-cell line HMC-1. Scand J Immunol. 1994 May;39(5):489–498. doi: 10.1111/j.1365-3083.1994.tb03404.x. [DOI] [PubMed] [Google Scholar]
  47. Pertovaara L., Saksela O., Alitalo K. Enhanced bFGF gene expression in response to transforming growth factor-beta stimulation of AKR-2B cells. Growth Factors. 1993;9(1):81–86. doi: 10.3109/08977199308991584. [DOI] [PubMed] [Google Scholar]
  48. Pesci A., Bertorelli G., Gabrielli M., Olivieri D. Mast cells in fibrotic lung disorders. Chest. 1993 Apr;103(4):989–996. doi: 10.1378/chest.103.4.989. [DOI] [PubMed] [Google Scholar]
  49. Qu Z., Liebler J. M., Powers M. R., Galey T., Ahmadi P., Huang X. N., Ansel J. C., Butterfield J. H., Planck S. R., Rosenbaum J. T. Mast cells are a major source of basic fibroblast growth factor in chronic inflammation and cutaneous hemangioma. Am J Pathol. 1995 Sep;147(3):564–573. [PMC free article] [PubMed] [Google Scholar]
  50. Quarto N., Finger F. P., Rifkin D. B. The NH2-terminal extension of high molecular weight bFGF is a nuclear targeting signal. J Cell Physiol. 1991 May;147(2):311–318. doi: 10.1002/jcp.1041470217. [DOI] [PubMed] [Google Scholar]
  51. Reed J. A., Albino A. P., McNutt N. S. Human cutaneous mast cells express basic fibroblast growth factor. Lab Invest. 1995 Feb;72(2):215–222. [PubMed] [Google Scholar]
  52. Rifkin D. B., Moscatelli D. Recent developments in the cell biology of basic fibroblast growth factor. J Cell Biol. 1989 Jul;109(1):1–6. doi: 10.1083/jcb.109.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Ruoss S. J., Hartmann T., Caughey G. H. Mast cell tryptase is a mitogen for cultured fibroblasts. J Clin Invest. 1991 Aug;88(2):493–499. doi: 10.1172/JCI115330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Saldiva P. H., Delmonte V. C., de Carvalho C. R., Kairalla R. A., Auler Júnior J. O. Histochemical evaluation of lung collagen content in acute and chronic interstitial diseases. Chest. 1989 May;95(5):953–957. doi: 10.1378/chest.95.5.953. [DOI] [PubMed] [Google Scholar]
  55. Schiltz P. M., Lieber J., Giorno R. C., Claman H. N. Mast cell immunohistochemistry: non-immunological immunostaining mediated by non-specific F(ab')2-mast cell secretory granule interaction. Histochem J. 1993 Sep;25(9):642–647. doi: 10.1007/BF00157878. [DOI] [PubMed] [Google Scholar]
  56. Schwartz L. B., Bradford T. R. Regulation of tryptase from human lung mast cells by heparin. Stabilization of the active tetramer. J Biol Chem. 1986 Jun 5;261(16):7372–7379. [PubMed] [Google Scholar]
  57. Stopa E. G., Gonzalez A. M., Chorsky R., Corona R. J., Alvarez J., Bird E. D., Baird A. Basic fibroblast growth factor in Alzheimer's disease. Biochem Biophys Res Commun. 1990 Sep 14;171(2):690–696. doi: 10.1016/0006-291x(90)91201-3. [DOI] [PubMed] [Google Scholar]
  58. Takizawa H., Ohta K., Hirai K., Misaki Y., Horiuchi T., Kobayashi N., Shiga J., Miyamoto T. Mast cells are important in the development of hypersensitivity pneumonitis. A study with mast-cell-deficient mice. J Immunol. 1989 Sep 15;143(6):1982–1988. [PubMed] [Google Scholar]
  59. Tazawa S., Hayakawa Y., Ishikawa T., Niiya K., Sakuragawa N. Heparin stimulates the proliferation of bovine aortic endothelial cells probably through activation of endogenous basic fibroblast growth factor. Thromb Res. 1993 Dec 1;72(5):431–439. doi: 10.1016/0049-3848(93)90243-h. [DOI] [PubMed] [Google Scholar]
  60. Vlodavsky I., Fuks Z., Ishai-Michaeli R., Bashkin P., Levi E., Korner G., Bar-Shavit R., Klagsbrun M. Extracellular matrix-resident basic fibroblast growth factor: implication for the control of angiogenesis. J Cell Biochem. 1991 Feb;45(2):167–176. doi: 10.1002/jcb.240450208. [DOI] [PubMed] [Google Scholar]
  61. Walls A. F., Roberts J. A., Godfrey R. C., Church M. K., Holgate S. T. Histochemical heterogeneity of human mast cells: disease-related differences in mast cell subsets recovered by bronchoalveolar lavage. Int Arch Allergy Appl Immunol. 1990;92(3):233–241. doi: 10.1159/000235183. [DOI] [PubMed] [Google Scholar]
  62. Watters L. C., Schwarz M. I., Cherniack R. M., Waldron J. A., Dunn T. L., Stanford R. E., King T. E. Idiopathic pulmonary fibrosis. Pretreatment bronchoalveolar lavage cellular constituents and their relationships with lung histopathology and clinical response to therapy. Am Rev Respir Dis. 1987 Mar;135(3):696–704. doi: 10.1164/arrd.1987.135.3.696. [DOI] [PubMed] [Google Scholar]
  63. Willcox M., Kervitsky A., Watters L. C., King T. E., Jr Quantification of cells recovered by bronchoalveolar lavage. Comparison of cytocentrifuge preparations with the filter method. Am Rev Respir Dis. 1988 Jul;138(1):74–80. doi: 10.1164/ajrccm/138.1.74. [DOI] [PubMed] [Google Scholar]
  64. Yamanaka Y., Friess H., Buchler M., Beger H. G., Uchida E., Onda M., Kobrin M. S., Korc M. Overexpression of acidic and basic fibroblast growth factors in human pancreatic cancer correlates with advanced tumor stage. Cancer Res. 1993 Nov 1;53(21):5289–5296. [PubMed] [Google Scholar]
  65. Yamashita Y., Nakagomi K., Takeda T., Hasegawa S., Mitsui Y. Effect of heparin on pulmonary fibroblasts and vascular cells. Thorax. 1992 Aug;47(8):634–639. doi: 10.1136/thx.47.8.634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Yayon A., Klagsbrun M., Esko J. D., Leder P., Ornitz D. M. Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor. Cell. 1991 Feb 22;64(4):841–848. doi: 10.1016/0092-8674(91)90512-w. [DOI] [PubMed] [Google Scholar]
  67. Yeh J., Osathanondh R. Expression of messenger ribonucleic acids encoding for basic fibroblast growth factor (FGF) and alternatively spliced FGF receptor in human fetal ovary and uterus. J Clin Endocrinol Metab. 1993 Nov;77(5):1367–1371. doi: 10.1210/jcem.77.5.8077334. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES